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Cosmetic 

Dermatology 

Products & Procedures 








Cosmetic Dermatology 

Products and Procedures 



Cosmetic 

Dermatology 

Products and 
Procedures 


EDITED BY 

Zoe Diana Draelos MD 


Consulting Professor 
Department of Dermatology 
Duke University School of Medicine 
Durham, North Carolina 
USA 


®WI LEY- BLACKWELL 

A John Wiley & Sons, Ltd., Publication 


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Library of Congress Cataloging-in-Publication Data 

Cosmetic dermatology : products and procedures / edited by Zoe Diana Draelos. 
p. ; cm. 

Includes bibliographical references and index. 

ISBN 978-1-4051-8635-3 (hardcover : alk. paper) 

1. Skin-Care and hygiene. 2. Cosmetics. 3. Dermatology. I. Draelos, Zoe Kececioglu. 

[DNLM: 1. Cosmetics. 2. Dermatologic Agents. 3. Cosmetic Techniques. 4. Skin Care- 
methods. QV 60 C8346 2009] 

RL87.C68 2009 
646.7'2-dc22 

2009031482 

ISBN: 9781405186353 

A catalogue record for this book is available from the British Library. 

Set in 9 on 12 pt Meridien by Toppan Best-set Premedia Limited 
Printed and bound in Singapore 


1 2010 


Contents 


Contributors, viii 

Foreword, xiv 
Jeffrey S. Dover 

Introduction: Definition of Cosmetic Dermatology, xv 
Zoe D. Draelos 


Section I Basic Concepts, 1 

Part One Skin Physiology Pertinent to Cosmetic 
Dermatology, 3 

1 Epidermal barrier, 3 

Sreekumar Pillai, Marc Cornell, and Christian Oresajo 

2 Photoaging, 13 

Murad Alam and Jillian Havey 

3 Self-perceived sensitive skin, 22 
Olivier de Lacharriere 

4 Pigmentation and skin of color, 27 
Chesahna Kindred and Rehat M. Haider 

5 Sensitive skin and the somatosensory system, 38 
Francis McGlone and David Reilly 

6 Novel, compelling non-invasive techniques for 
evaluating cosmetic products, 47 

Thomas J. Stephens, Christian Oresajo, Robert Goodman, 
Margarita Yatskayer, and Paul Kavanaugh 

1 Contact dermatitis and topical agents, 33 
David E. Cohen and Aieska de Souza 

Part Two Delivery of Cosmetic Skin Actives, 62 

8 Percutaneous delivery of cosmetic actives to the skin, 62 
Marc Cornell, Sreekumar Pillai, and Christian Oresajo 

9 Creams, lotions, and ointments, 71 
Irwin Palefsky 


Section II Hygiene Products, 75 

Part One Cleansers, 77 

10 Bar cleansers, 77 

Anthony W. Johnson and K.P. Ananthapadmanabhan 

11 Personal cleansers: body washes, 88 
Keith Ertel and Heather Focht 

12 Facial cleansers and cleansing cloths, 95 
Erik Hasenoehrl 

13 Non-foaming and low-foaming cleansers, 102 
Duncan Aust 

14 Liquid hand cleansers and sanitizers, 106 
Duane Charbonneau 

15 Shampoos for normal scalp hygiene and dandruff, 115 
James R. Schwartz, Marcela Valenzuela, and Sanjeev Midha 

Part Two Moisturizers, 123 

16 Facial moisturizers, 123 
Yohini Appa 

17 Hand and foot moisturizers, 130 

Teresa M. Weber, Andrea M. Schoelermann, Ute Breitenbach, 
Ulrich Scherdin, and Alexandra Kowcz 

18 Sunless tanning products, 139 

Angelike Galdi, Peter Foltis, and Christian Oresajo 

19 Sunscreens, 144 

Dominique Moyal, Angelike Galdi, and Christian Oresajo 

Part Three Personal Care Products, 150 

20 Antiperspirants and deodorants, 150 
Eric S. Abrutyn 

21 Blade shaving, 156 

Keith Ertel and Gillian McFeat 


v 


Contents 


Section III Adornment, 165 

Part One Colored Facial Cosmetics, 167 

22 Facial foundation, 167 

Sylvie Guichard and Veronique Roulier 

23 Camouflage techniques, 176 
Anne Bouloc 

24 Lips and lipsticks, 184 

Catherine Heusele, Herve Cantin, and Frederic Bonte 

25 Eye cosmetics, 190 

Sarah A. Vickery Peter Wyatt, and John Gilley 

Part Two Nail Cosmetics, 197 

26 Nail physiology and grooming, 197 
Phoebe Rich and Heh Shin R. Kwak 

27 Colored nail cosmetics and hardeners, 206 
Paul H. Bryson and Sunil J. Sirdesai 

28 Cosmetic prostheses as artificial nail enhancements, 215 
Douglas Schoon 

Part Three Hair Cosmetics, 222 

29 Hair physiology and grooming, 222 

Maria Hordinsky, Ana Paula Avancini Caramori, and 
Jeff D. Donovan 

30 Hair dyes, 227 

Frauke Neuser and Harald Schlatter 

31 Permanent hair waving, 236 

Annette Schwan-Jonczyk and Gerhard Sendelbach 

32 Hair straightening, 248 

Harold Bryant, Felicia Dixon, Angela Ellington, and 
Crystal Porter 

33 Hair styling - technology and formulations, 256 
Thomas Krause, Rene Rust, and Dianna C. Kenneally 

Section IV Antiaging, 267 

Part One Cosmeceuticals, 269 

34 Botanicals, 269 
Carl Thornfeldt 

35 Antioxidants and anti-inflammatories, 281 
Bryan B. Fuller 

36 Peptides and proteins, 292 
Karl Lintner 

37 Cellular growth factors, 302 

Richard E. Fitzpatrick and Rahul C. Mehta 


38 Retinoids, 309 

Olivier Sorg, Giirkan Kay a, Behrooz Kasraee, and 
Jean H. Saurat 

39 Topical vitamins, 319 
Donald L. Bissett 

40 Clinical uses of hydroxyacids, 327 

Barbara Green, Eugene J. Van Scott, and Ruey Yu 

41 The contribution of dietary nutrients and supplements 
to skin health, 335 

Helen Knaggs, Steve Wood, Doug Burke, and Jan Lephart 

Part Two Injectable Antiaging Techniques, 342 

42 Botulinum toxins, 342 

Joel L. Cohen and Scott R. Freeman 

43 Hyaluronic acid fillers, 352 
Mark S. Nestor 

44 Calcium hydroxylapatite for soft tissue augmentation, 356 
Stephen Mandy 

45 Skin fillers, 361 

Neil Sadick, Misbah H. Khan, and Babar K. Rao 

46 Polylactic acid fillers, 373 
Kenneth R. Beer 

Part Three Resurfacing Techniques, 377 

47 Superficial chemical peels, 377 

M. Amanda Jacobs and Randall Roenigk 

48 Medium depth chemical peels, 384 
Gary D. Monheit and Jens J. Thiele 

49 C0 2 laser resurfacing: confluent and fractionated, 393 
Mitchel P. Goldman 

50 Non-ablative resurfacing, 409 
David J. Goldberg and Katie Rossy 

51 Microdermabrasion, 418 
Pearl Grimes 

52 Dermabrasion, 426 

Christopher Harmon and Chad Prather 

Part Four Skin Modulation Techniques, 432 

53 Laser-assisted hair removal, 432 

Keyvan Nouri, Voraphol Vejjabhinanta, Nidhi Avashia, and 
Rawat Charoensawad 

54 Radiofrequency devices, 439 
Vic Narurkar 

55 LED photomodulation for reversal of photoaging and 
reduction of inflammation, 444 

Robert Weiss, Roy Geronemus, David McDaniel, and 
Corinne Granger 


VI 


Contents 


Part Five Skin Contouring Techniques, 450 

56 Liposuction: manual, mechanical, and laser assisted, 450 
Emily Tierney and C. William Hanke 

57 Liposuction of the neck, 463 
Kimberly J. Butterwick 

58 Hand recontouring with calcium hydroxylapatite, 473 
Kenneth L. Edelson 

Part Six Implementation of Cosmetic Dermatology into 
Therapeutics, 480 

59 Antiaging regimens, 480 
Karen E. Burke 


60 Over-the-counter acne treatments, 488 
Emmy M. Graber and Diane Thiboutot 

61 Rosacea regimens, 495 
Joseph Bikowski 

62 Eczema regimens, 502 
Zoe D. Draelos 

63 Psoriasis regimens, 507 

Steven R. Feldman and Lindsay C. Strowd 

Index, 514 


VII 


Contributors 


Eric S. Abrutyn ms 

Founder 

TPC2 Advisors Ltd. Inc. 

Chiriqui, Republic of Panama 

Murad Alam md, msci 

Associate Professor of Dermatology and Otolaryngology 

Chief of Cutaneous and Aesthetic Surgery 

Department of Dermatology 

Feinberg School of Medicine 

Northwestern University 

Chicago, IL, USA 

K.P. Ananthapadmanabhan phd 

Senior Principal Scientist 
Unilever HPC R&D 
Trumbull, CT, USA 

Yohini Appa phd 

Senior Director of Scientific Affairs, 

Johnson & Johnson 
New Brunswick, NJ, USA 

Duncan Aust phd 

Senior Vice President of Research and Development 
DFB Branded Pharmaceuticals 
Fort Worth, TX, USA 

Nidhi Avashia md 

Department of Dermatology and Cutaneous Surgery 
University of Miami Miller School of Medicine 
Miami, FL, USA 

Kenneth R. Beer md, pa 

Palm Beach Esthetic, Dermatology & Laser Center 

West Palm Beach, FL, USA 

and 

Clinical Voluntary Assistant Professor of Dermatology 
University of Miami 
Miami, FL, USA 

Joseph Bikowski md, faad 

Clinical Assistant Professor, Dermatology 
Ohio State University 
Columbus, OH, USA 
and 

Bikowski Skin Care Center 
Sewickley, PA, USA 


Donald L. Bissett phd 

Beth Jewell-Motz 
Procter & Gamble Co. 

Sharon Woods Technical Center 
Cincinnati, OH, USA 

Frederic Bonte phd 

Director of Scientific Communication 

LVMH Recherche 

Saint Jean de Braye, France 

Anne Bouloc md, phd 

Vichy International Medical Director 
Cosmetique Active International 
Asnieres, France 

Ute Breitenbach phd 

Beiersdorf AG 
Hamburg, Germany 

Harold Bryant phd 

Assistant Vice President 

L'Oreal Institute for Ethnic Hair and Skin Research 
Chicago, IL, USA 

Paul H. Bryson phd 

Director of Research and Development 
OPI Products Inc. 

North Hollywood 
Los Angeles, CA, USA 

Doug Burke phd 

Senior Scientist 

Phamanex Global Research and Development 
Provo, UT, USA 

Karen E. Burke md, phd 

Assistant Clinical Professor, Dermatology 
The Mount Sinai Medical Center 
Rivercourt 
New York, NY, USA 

Kimberly J. Butterwick md 

Dermatology/Cosmetic Laser Associates of La Jolla, Inc. 
San Diego, CA, USA 


viii 


Contributors 


Herve Cantin 

LVMH Recherche 

Saint Jean de Braye, France 

Ana Paula Avancini Caramori md 

Department of Dermatology 

Complexo Hospitalar Santa Casa de Porto Alegre 

Porto Alegre, Brazil 

Duane Charbonneau phd 

Global Microbiology 
Procter & Gamble Co. 

Health Sciences Institute 
Mason, OH, USA 

Rawat Charoensawad md 

Director, Rawat Clinic and 

Clinical Consultant, Biophile Training Center 

Bangkok, Thailand 

David E. Cohen, md, mph 

Vice Chairman for Clinical Affairs 

Director of Allergic, Occupational, and Environmental Dermatology 
New York University School of Medicine 
Department of Dermatology 
New York, NY, USA 

Joel L. Cohen md 

About Skin Dermatology 
Englewood, CO, USA 
and 

Department of Dermatology 
University of Colorado 
Englewood, CO, USA 

Marc Cornell 

Director 

L'Oreal Research 
Clark, NJ, USA 

Felicia Dixon phd 

Manager 

L'Oreal Institute for Ethnic Hair and Skin Research 
Chicago, IL, USA 

Jeff C. Donovan md, phd 

Division of Dermatology 
University of Toronto 
Toronto, Canada 

Jeffrey S. Dover md, frcpc, frcp (Glasgow) 

Associate Clinical Professor of Dermatology 
Yale University School of Medicine, 

Adjunct Professor of Dermatology 
Dartmouth Medical School, 

SkinCare Physicians 
Chestnut Hill, MA, USA 


Zoe D. Draelos md 

Consulting Professor 
Department of Dermatology 
Duke University School of Medicine 
Durham, NC, USA 

Kenneth L. Edelson md, faacs 

Clinical Instructor, Department of Dermatology 
Mount Sinai School of Medicine 

Attending Physician, Dermatology, The Mount Sinai Hospital 
New York, NY, USA and 
Private Practice 

Cosmetic, Dermatologic and Laser Surgery 
New York, NY, USA 

Angela Ellington 

Assistant Vice President 

L'Oreal Institute for Ethnic Hair and Skin Research 
Chicago, IL, USA 

Keith Ertel ms, phd 

Principal Scientist 
Procter & Gamble Co. 

Cincinnati, OH, USA 

Steven R. Feldman md, phd 

Center for Dermatology Research 

Departments of Dermatology, Pathology, and Public Health Sciences 
Wake Forest University School of Medicine 
Winston-Salem, NC, USA 

Richard E. Fitzpatrick md 

Founder, Chair, Scientific Advisory Board 
SkinMedica, Inc. 

Carlsbad, CA, USA 
and 

Associate Clinical Professor 
Division of Dermatology 
UCSD School of Medicine 
San Diego, CA, USA 

Heather Focht ma 

Section Head 
Procter & Gamble Co. 

Cincinnati, OH, USA 

Peter Foltis ms 

Director of Scientific Affairs and Skin Care 
L'Oreal USA 
Clark, NJ, USA 

Scott R. Freeman md 

Dermatology Resident 

University of Colorado at Denver and Health Sciences Center 
Denver, CO, USA 


IX 


Contributors 


Bryan B. Fuller phd 

Founder, CEO 

Therametics 

and 

Adjunct Professor of Biochemistry and Molecular Biology 
University of Oklahoma Health Sciences Center 
Oklahoma City, OK, USA 

Angelike Galdi ms 

L'Oreal USA 
Clark, NJ, USA 

Roy Geronemus md 

Laser & Skin Surgery Center of New York 

New York, NY, USA 

and 

New York University Medical Center 
New York, NY, USA 

John Gilley 

Principal Researcher 
Procter & Gamble Cosmetics 
Hunt Valley, MD, USA 

David J. Goldberg md 

Clinical Professor and Director of Laser Research 

Department of Dermatology at the Mount Sinai School of Medicine 

New York, NY, USA 

and 

Director, Skin Laser & Surgery Specialists of New York and New Jersey 
New York, NY, USA 

Mitchel P. Goldman md 

Volunteer Clinical Professor of Dermatology/Medicine 
University of California, San Diego and 

Dermatology/Cosmetic Dermatology Associates of La Jolla, Inc. 

San Diego, CA, USA 

Robert Goodman 

Thomas J. Stephens & Associates Inc. 

Dallas Research Center 
Carrollton, TX, USA 

Emmy M. Graber md 

SkinCare Physicians 
Chestnut Hill, MA, USA 

Corinne Granger md 

Director of Instrumental Cosmetics 
L'Oreal Research 
Asnieres, France 

Barbara A. Green rph, ms 

VP Clinical Affairs, NeoStrata Company, Inc. 

Princeton, NJ, USA 


Pearl Grimes md 

Director 

Vitiligo and Pigmentation Institute of Southern California 

Los Angeles, CA, USA 

and 

Clinical Professor 
Division of Dermatology 
David Geffen School of Medicine 
University of California-Los Angeles 
Los Angeles, CA, USA 

Sylvie Guichard 

Make Up Scientific Communication Director 
L'Oreal Recherche 
Chevilly-Larue, France 

Rebat M. Haider md 

Professor and Chair 
Department of Dermatology 
Howard University College of Medicine 
Washington, DC, USA 

C. William Hanke md, mph, facp 

Professor of Dermatology 
University of Iowa 
Carver College of Medicine 
Iowa City, IA, USA 
and 

Clinical Professor of Otolaryngology-Head and Neck Surgery 
Indiana University School of Medicine 
Indianapolis, IN, USA 

Christopher Harmon md 

Total Skin and Beauty Dermatology Center 
Birmingham, AL, USA 

Erik Hasenoehrl phd 

Procter & Gamble Co. 

Ivory dale Technical Center 
Cincinnati, OH, USA 

Jillian Havey 

Department of Dermatology 
Feinberg School of Medicine 
Northwestern University 
Chicago, IL, USA 

Catherine Heusele 

LVMH Recherche 

Saint Jean de Braye, France 

Maria Hordinsky md 

Professor and Chair 
Department of Dermatology 
University of Minnesota 
Minneapolis, MN, USA 

M. Amanda Jacobs md 

Senior Associate Consultant 
Department of Dermatology 
Mayo Clinic 
Rochester, MN, USA 


x 


Anthony W. Johnson phd 

Director, Skin Clinical Science 
Unilever HPC R&D 
Trumbull, CT, USA 

Behrooz Kasraee md 

Department of Dermatology 
Geneva University Hospital 
Geneva, Switzerland 

Paul Kavanaugh ms 

Thomas J. Stephens & Associates Inc. 

Dallas Research Center 
Carrollton, TX, USA 

Giirkan Kaya md, phd 

Department of Dermatology 
Geneva University Hospital 
Geneva, Switzerland 

Dianna C. Kenneally che 

Principal Scientist 
Procter & Gamble Co. 

Mason, OH, USA 

Misbah H. Khan md 

Fellow, Procedural Dermatology 
Northwestern University and 
Northwestern Memorial Hospital 
Chicago, IL, USA 

Chesahna Kindred md, mba 

Clinical Research Fellow 
Department of Dermatology 
Howard University College of Medicine 
Washington, DC, USA 

Helen Knaggs phd 

Vice President 

Nu Skin Global Research and Development 
Provo, UT, USA 

Alexandra Kowcz ms, mba 

VP, US R&D 
Beiersdorf Inc. 

Wilton, CT, USA 

Thomas Krause phd 

Polymer Chemist 

Wella/Procter & Gamble Service GmbH 
Upstream Design Styling 
Darmstadt, Germany 

Heh Shin R. Kwak md 

Knott Street Dermatology 
301 NW Knott Street 
Portland, OR, USA 


Jan Lephart 

Senior Director 

Nu Skin Global Research & Development 
Provo, UT, USA 

Karl Lintner msc, phd 

Technical Advisor 

Enterprise Technology/Sederma SAS 
Le Perray en Yvelines 
Cedex, France 

Stephen Mandy md 

Volunteer Professor of Dermatology 
University of Miami 
Miami, FL, USA 
and 

Private Practice 
Miami Beach, FL, USA 

David McDaniel md 

Laser Skin & Vein Center of Virginia 

Virginia Beach, VA, USA 

and 

Eastern Virginia Medical School 
Virginia Beach, VA, USA 

Gillian McFeat phd 

Gillette Reading Innovation Centre 
Procter & Gamble Co. 

Reading, UK 

Francis McGlone phd 

Perception and Behaviour Group 
Unilever Research & Development 
Wirral, UK 

Rahul C. Mehta phd 

Senior Scientific Director 
SkinMedica, Inc. 

Carlsbad, CA, USA 

Sanjeev Midha phd 

Principal Scientist 

Procter & Gamble Beauty Science 

Cincinnati, OH, USA 

Gary D. Monheit md 

Total Skin & Beauty Dermatology Center, PC, and 
Clinical Associate Professor 
Departments of Dermatology and Ophthamology 
University of Alabama at Birmingham 
Birmingham, AL, USA 

Dominique Moyal phd 

L'Oreal Recherche 
Asnieres, France 


Olivier de Lacharriere md, phd 

L'Oreal Recherche 
Clichy, France 


Contributors 


Vic Narurkar md, faad 

Director 

Bay Area Laser Institute 
San Francisco, CA, USA 
and 

University of California Davis Medical School 
Sacramento, CA, USA 

Mark S. Nestor md, phd 

Director 

Center for Cosmetic Enhancement 

Aventura, FL, USA 

and 

Voluntary Associate Professor of Dermatology and Cutaneous Surgery 
University of Miami 
Miller School of Medicine 
Miami, FL, USA 

Frauke Neuser PhD 

Principal Scientist 

Procter & Gamble Technical Centres Ltd 
Rusham Park, Whitehall Lane 
Egham 
Surrey, UK 

Keyvan Nouri md 

Professor of Dermatology and Otolaryngology 
Director of Mohs, Dermatologic and Laser Surgery 
Director of Surgical Training 

Department of Dermatology and Cutaneous Surgery 
University of Miami Miller School of Medicine 
Miami, FL, USA 

Christian Oresajo phd 

Assistant Vice President 
L'Oreal USA 
Clark, NJ, USA 

Irwin Palefsky 

CEO 

Cosmetech Laboratories Inc. 

Fairfield, NJ, USA 

Sreekumar Pillai phd 

Associate Principal Scientist 
L'Oreal Research 
Clark, NJ, USA 

Crystal Porter phd 

Manager 

L'Oreal Institute for Ethnic Hair and Skin Research 
Chicago, IL, USA 

Chad Prather md 

Total Skin and Beauty Dermatology Center 
Birmingham, AL, USA 


Babar K. Rao md 

Chair 

Department of Dermatology 
University of Medicine and Dentistry New Jersey 
Robert-Wood Johnson Medical School 
Somerset, NJ, USA 

David Reilly phd 

One Discover 
Colworth Park 
Sharnbrook 
Bedford, UK 

Phoebe Rich md 

Oregon Dermatology and Research Center 
Portland, OR, USA 

Randall Roenigk md 

Robert H. Kieckhefer Professor, Chair 
Department of Dermatology 
Mayo Clinic 
Rochester, MN, USA 

Katie Rossy md 

New York Medical College 
New York, NY, USA 

Veronique Roulier 

Make Up Development Director 
L'Oreal Recherche 
Chevilly-Larue, France 

Rene Rust phd 

Senior Scientist, Hair and Scalp Care 
Wella/Procter & Gamble Service GmbH 
Darmstadt, Germany 


Neil Sadick md, faad, faacs, facph 

Clinical Professor 

Weill Cornell Medical College 

New York, NY, USA 

and 

Sadick Dermatology 
New York, NY, USA 

Jean H. Saurat md 

Department of Dermatology 
Geneva University Hospital 
Geneva, Switzerland 

Ulrich Scherdin phd 

Beiersdorf AG 
Hamburg, Germany 

Andrea M. Schoelermann phd 

Beiersdorf AG 
Hamburg, Germany 

Harald Schlatter phd 

Principal Toxicologist 

Procter & Gamble German Innovation Centre 
Darmstadt, Germany 


XII 


Douglas Schoon 

Schoon Scientific and Regulatory Consulting, LLC 
Dana Point, CA, USA 

Annette Schwan-Jonczyk phd 

Wella/Procter & Gamble Service GmbH 
Global Hair Methods 
Darmstadt, Germany 

James R. Schwartz phd 

Research Fellow 

Procter & Gamble Beauty Science 
Cincinnati, OH, USA 

Gerhard Sendelbach phd 

Wella/Procter & Gamble Service GmbH 
Global Hair Methods 
Darmstadt, Germany 

Sunil J. Sirdesai phd 

Co-Director of Research and Development 
OPI Products Inc. 

North Hollywood 
Los Angeles, CA, USA 

Olivier Sorg phd 

Department of Dermatology 
Geneva University Hospital 
Geneva, Switzerland 

Aieska de Souza md, msc 

New York University School of Medicine 
Department of Dermatology 
New York, NY, USA 

Thomas J. Stephens phd 

Thomas J. Stephens & Associates Inc. 

Dallas Research Center 
Carrollton, TX, USA 

Lindsay C. Strowd md 

Center for Dermatology Research 
Department of Dermatology 
Wake Forest University School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC, USA 

Diane Thiboutot md 

Pennsylvania State University College of Medicine 
Milton S. Hershey Medical Center 
Hershey, PA, USA 

Jens J. Thiele md, phd 

Dermatology Specialist, Inc. 

Oceanside, CA, USA 

Carl Thornfeldt md, faad 

CTDerm, PC 
Fruitland, ID, USA and 
Episciences, Inc. 

Boise, ID, USA 


Emily Tierney phd 

Mohr Surgery and Procedural Dermatology Fellow 
Laser and Skin Surgery Center of Indiana 
Carmel, IN, USA 
and 

Department of Dermatology 
Boston University School of Medicine 
Boston, MA, USA 

Marcela Valenzuela phd 

Senior Scientist 

Procter & Gamble Beauty Science 
Cincinnati, OH, USA 

Eugene J. Van Scott md 

Private Practice 
Abington, PA, USA 

Voraphol Vejjabhinanta md 

Clinical instructor 

Suphannahong Dermatology Institute 
Bangkok, Thailand and 

Mohs, Dermatologic and Laser Surgery Fellow 
Department of Dermatology and Cutaneous Surgery 
University of Miami Miller School of Medicine 
Miami, FL, USA 

Sarah A. Vickery phd 

Principal Scientist 
Procter & Gamble Cosmetics 
Hunt Valley, MD, USA 

Teresa M. Weber phd 

Director, Clinical and Scientific Affairs 
Beiersdorf Inc. 

Wilton, CT, USA 

Robert Weiss md 

Maryland Laser Skin & Vein Institute 

Hunt Valley, MD, USA 

and 

Johns Hopkins University School of Medicine 
Baltimore, MD, USA 

Steve Wood phd 

Director 

Phamanex Global Research and Development 
Provo, UT, USA 

Peter Wyatt 

Senior Engineer 

Procter & Gamble Cosmetics 

Hunt Valley, MD, USA 

Margarita Yatskayer ms 

L'Oreal Research USA 
Clark, NJ, USA 

Ruey J. Yu phd, omd 

Private Practice 
Chalfont, PA, USA 


Foreword 


Dermatology began as a medical specialty but over the last 
half century it has evolved to combine medical and surgical 
aspects of skin care. Mohs skin cancer surgery was the cata¬ 
lyst that propelled dermatology to become a more procedur- 
ally based specialty. The combination of an aging population, 
economic prosperity, and technological breakthroughs have 
revolutionized cosmetic aspects of dermatology in the past 
few years. Recent minimally invasive approaches have 
enhanced our ability to prevent and reverse the signs of 
photoaging in our patients. Dermatologists have pioneered 
medications, technologies, and devices in the burgeoning 
field of cosmetic surgery. Cutaneous lasers, light, and energy 
sources, the use of botulinum exotoxin, soft tissue augmen¬ 
tation, minimally invasive leg vein treatments, chemical 
peels, hair transplants, and dilute anesthesia liposuction 
have all been either developed or improved by dermatolo¬ 
gists. Many scientific papers, reviews and textbooks have 
been published to help disseminate this new knowledge. 

Recently it has become abundantly clear that unless pho¬ 
toaging is treated with effective skin care and photoprotec¬ 
tion, cosmetic surgical procedures will not have their optimal 
outcome. Cosmeceuticals are integral to this process but, 
while some rigorous studies exist, much of the knowledge 
surrounding cosmeceuticals is hearsay and non-data based 
marketing information. Given increasing requests by our 
patients for guidance on the use of cosmeceuticals, under¬ 
standing this body of information is essential to the practic¬ 
ing dermatologist. 

In Cosmetic Dermatology: Products and Procedures , Zoe Draelos 
has compiled a truly comprehensive book that addresses the 
broad nature of the subspecialty. Unlike prior texts on the 


subject she has included all the essential topics of skin 
health. The concept is one that has been long awaited and 
will be embraced by our dermatologic colleagues and other 
health care professionals who participate in the diagnosis, 
and treatment of the skin. 

No one is better suited to edit a textbook of this scope than 
Dr. Zoe Draelos. She is an international authority on 
Cosmetic Dermatology and she has been instrumental in 
advancing the field of cosmeceuticals by her extensive 
research, writing, and teachings. This text brings together 
experts from industry, manufacturing, research, and derma¬ 
tology and highlights the best from each of these fields. 

Doctor Draelos has divided the book into four different 
segments. The book opens with Basic Concepts , which includes 
physiology pertinent to cosmetic dermatology, and delivery 
of cosmetic skin actives. This section is followed by Hygiene 
Products , which include cleansers, moisturizers, and personal 
care products. The section on Adornment includes colored 
facial products, nail cosmetics, and hair cosmetics. The 
book concludes with a section on Antiaging , which includes 
cosmeceuticals, injectable antiaging techniques, resurfacing 
techniques, and skin modulation techniques. 

You will enjoy dipping into individual chapters or sections 
depending on your desires, but a full read of the book from 
start to finish will no doubt enhance your knowledge base 
and prepare you for the full spectrum of cosmetic dermatol¬ 
ogy patients. 

Enjoy. 

Jeffrey S. Dover 
August 2009 


XIV 


Introduction: Definition of Cosmetic Dermatology 


This text is intended to function as a compendium on the 
field of cosmetic dermatology. Cosmetic dermatology knowl¬ 
edge draws on the insight of the bench researcher, the 
innovation of the manufacturer, the formulation expertise 
of the cosmetic chemist, the art of the dermatologic surgeon, 
and the experience of the clinical dermatologist. These 
knowledge bases heretofore have been presented in separate 
textbooks written for specific audiences. This approach to 
information archival does not provide for the synthesis of 
knowledge required to advance the science of cosmetic 
dermatology. 

The book begins with a discussion of basic concepts relat¬ 
ing to skin physiology. The areas of skin physiology that are 
relevant to cosmetic dermatology include skin barrier, pho¬ 
toaging, sensitive skin, pigmentation issues, and sensory 
perceptions. All cosmetic products impact the skin barrier, 
it is to be hoped in a positive manner, to improve skin 
health. Failure of the skin to function optimally results in 
photoaging, sensitive skin, and pigmentation abnormalities. 
Damage to the skin is ultimately perceived as sensory 
anomalies. Skin damage can be accelerated by products 
that induce contact dermatitis. While the dermatologist 
can assess skin health visually, non-invasive methods are 
valuable to confirm observations or to detect slight changes 
in skin health that are imperceptible to the human eye. 

An important part of cosmetic dermatology products is the 
manner in which they are presented to the skin surface. 
Delivery systems are key to product efficacy and include 
creams, ointments, aerosols, powders, and nanoparticles. 
Once delivered to the skin surface, those substances designed 
to modify the skin must penetrate with aid of penetration 
enhancers to ensure percutaneous delivery. 

The most useful manner to evaluate products used in 
cosmetic dermatology is by category. The book is organized 
by product, based on the order in which they are used as 
part of a daily routine. The first daily activity is cleansing to 
ensure proper hygiene. A variety of cleansers are available 
to maintain the biofilm to include bars, liquids, non¬ 
foaming, and antibacterial varieties. They can be applied 
with the hands or with the aid of an implement. Specialized 
products to cleanse the hair are shampoos, which may be 
useful in prevention of scalp disease. 

Following cleansing, the next step is typically moisturiza- 
tion. There are unique moisturizers for the face, hands, and 
feet. Extensions of moisturizers that contain other active 


ingredients include sunscreens. Other products with a 
unique hygiene purpose include antiperspirants and shaving 
products. This completes the list of major products used to 
hygiene and skincare purposes. 

The book then turns to colored products for adorning the 
body. These include colored facial cosmetics, namely facial 
foundations, lipsticks, and eye cosmetics. It is the artistic use 
of these cosmetics that can provide camouflaging for skin 
abnormalities of contour and color. Adornment can also be 
applied to the nails, in the forms of nail cosmetics and pros- 
theses, and to the hair, in the form of hair dyes, permanent 
waves, and hair straightening. 

From adornment, the book addresses the burgeoning 
category of cosmeceuticals. Cosmeceuticals can be divided 
into the broad categories of botanicals, antioxidants, anti¬ 
inflammatories, peptides and proteins, cellular growth 
factors, retinoids, exfoliants, and nutraceuticals. These 
agents aim to improve the appearance of aging skin through 
topical applications, but injectable products for rejuvenation 
are an equally important category in cosmetic dermatology. 
Injectables can be categorized as neurotoxins and fillers 
(hyaluronic acid, hydroxyapatite, collagen, and polylactic 
acid). 

Finally, the surgical area of cosmetic dermatology must be 
address in terms of resurfacing techniques, skin modulation 
techniques, and skin contouring techniques. Resurfacing 
can be accomplished chemically with superficial and 
medium depth chemical peels or physically with microder¬ 
mabrasion and dermabrasion. The newest area of resurfac¬ 
ing involves the use of lasers, both ablative and non-ablative. 
Other rejuvenative devices than collagen and pigmentation 
include intense pulsed light, radiofrequency, and diodes. 
These techniques can be combined with liposuction of the 
body and face to recontour the adipose tissue underlying 
the skin. 

The book closes with a discussion of how cosmetic der¬ 
matology can be implemented as part of a treatment regimen 
for aging skin, acne, rosacea, psoriasis, and eczema. In order 
to allow effective synthesis of the wide range of information 
included in this text, each chapter has been organized 
with a template to create a standardized presentation. The 
chapters open with basic concepts pertinent to each area. 
From these key points, the authors have developed their 
information to define the topic, discuss unique attributes, 
advantages and disadvantages, and indications. 


xv 


Introduction 


It is my hope that this book will provide a standard text¬ 
book for the broad field of cosmetic dermatology. In the past, 
cosmetic dermatology has been considered a medical and 
surgical afterthought in dermatology residency programs 
and continuing medical education sessions. Perhaps this was 
in part because of the lack of a textbook defining the knowl¬ 


edge base. This is no longer the case. Cosmetic dermatology 
has become a field unto itself. 

Zoe D. Draelos 
May 2009 


XVI 


Section I 

Basic Concepts 





Part 1: Skin Physiology Pertinent to 
Cosmetic Dermatology 


Chapter 1: Epidermal barrier 

Sreekumar Pillai, Marc Cornell, and Christian Oresajo 

L'Oreal Research, Clark, NJ, USA 


BASIC CONCEPTS 

• The outer surface of the skin, the epidermis, along with its outermost layer, the stratum corneum, forms the epidermal barrier. 

• The stratum corneum is a structurally heterogeneous tissue composed of non-nucleated, flat, protein-enriched corneocytes and 
lipid-enriched intercellular domains. 

• The roles of the skin barrier include preventing microbes from entering the skin, protecting from environmental toxins, 
maintaining skin hydration, and diffusing oxidative stress. 

• Delivery technologies such as lipid systems, nanoparticles, microcapsules, polymers, and films can improve the barrier properties 
of the skin. 


Introduction 

Skin is the interface between the body and the environment. 
There are three major compartments of the skin: the epider¬ 
mis, the dermis, and the hypodermis. Epidermis is the out¬ 
ermost structure and it is a multilayered, epithelial tissue 
divided into several layers. The outermost structure of the 
epidermis is the stratum corneum (SC) which forms the 
epidermal permeability barrier that prevents the loss of 
water and electrolytes. Other protective or barrier roles for 
the epidermis include: immune defense, UV protection, and 
protection from oxidative damage. Changes in the epidermal 
barrier caused by environmental factors, age, or other condi¬ 
tions can alter the appearance as well as the functions of the 
skin. Understanding the structure and function of the SC 
and the epidermal barrier is vital because it is the key to 
healthy skin and its associated social ramifications. 


Structural components of the epidermal 
barrier 

The outer surface of the skin, the epidermis, mostly consists 
of epidermal cells, known as keratinocytes, which are 
arranged in several stratified layers - the basal cell layer, the 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


spinous cell layer and the granular cell layer - whose dif¬ 
ferentiation eventually produces the SC. Unlike other layers, 
the SC is made of anucleated cells called corneocytes which 
are derived from keratinocytes. The SC forms the major 
protective barrier of the skin, the epidermal permeability 
barrier. Figure 1.1 shows the different layers of the epider¬ 
mis and the components that form the epidermal barrier. 
The SC is a structurally heterogeneous tissue composed of 
non-nucleated, flat, protein-enriched corneocytes and lipid- 
enriched intercellular domains [1]. The lipids for barrier 
function are synthesized in the keratinocytes of the nucle¬ 
ated epidermal layers, stored in the lamellar bodies, and 
extruded into the intercellular spaces during the transition 
from the stratum granulosum to the SC forming a system of 
continuous membrane bilayers [1,2]. In addition to the 
lipids, other components such as melanins, proteins of the 
SC and epidermis, free amino acids and other small mole¬ 
cules also have important roles in the protective barrier of 
the skin. A list of the different structural as well as functional 
components of the SC is shown in Table 1.1. 

Corneocytes 

Corneocytes are formed by the terminal differentiation of 
the keratinocytes from the granular layer of the epidermis. 
The epidermis is comprised of 70% water, as are most tissues, 
yet the SC is comprised of only 15% water. Alongside this 
change in water content the keratinocyte nuclei and virtually 
all the subcellular organelles begin to disappear in the granu¬ 
lar cell layer leaving a proteineous core containing keratins, 
other structural proteins, free amino acids and amino acid 


3 









BASIC CONCEPTS Skin Physiology 


Keratohyalin and 
lamellar granules 
of the stratum 
granulosum 

Desmosomes- 

Melanocyte- 

Langerhans cell - 



Stratum corneum 
Stratum granulosum 

Stratum spinosum 

Stratum basale 

Dermis 


Figure 1.1 Diagram of the epidermis indicating 
the different layers of the epidermis and other 
structural components of the epidermal barrier. 


Table 1.1 Structural and functional components of the stratum corneum. 


Components 

Function 

Location 

SC 

Protection 

Topmost layer of epidermis 

CE 

Resiliency of SC 

Outer surface of the SC 

Cornified envelope 
precursor proteins 

Structural proteins that are 
cross-linked to form CE 

Outer surface of SC 

LG 

Permeability barrier of skin 

Granular cells of epidermis 

SC interfacial lipids 

Permeability barrier of skin 

Lipid bilayers between SC 

Lipid-protein cross-links 

Scaffold for corneocytes 

Between SC and lipid bi-layers 

Desmosomes and 

corneodesmosomes 

Intercellular adhesion and 
provide shear resistance 

Between keratinocytes and 
corneocytes 

Keratohyalin granules 

Formation of keratin "bundles" 
and NMF precursor proteins 

Stratum granulosum 

NMF 

Water holding capacity of SC 

Within SC 

pH and calcium gradients 

Provides differentiation signals 
and LG secretion signals 

All through epidermis 

Specialized enzymes 
(lipases, glycosidases, 
proteases) 

Processing and maturation of 

SC lipids, desquamation 

Within LG and all through 
epidermis 

Melanin granules and 
"dust" 

UV protection of skin 

Produced by melanocytes of 
basal layer, melanin "dust" in 

SC 


CE, cornified envelope; LG, lamellar granules; NMF, natural moisturizing factor; SC, stratum 
corneum. 


4 
















1. Epidermal barrier 


derivatives, and melanin particles which persist throughout 
the SC. From an oval or polyhedral shape of the viable cells 
in the spinous layers, the keratinocyte starts to flatten off in 
the granular cell layer and then assumes a spindle shape and 
finally becomes a flat corneocyte. The corneocyte itself 
develops a tough, chemically resistant protein band at the 
periphery of the cell, called the cornified cell envelope, 
formed from cross-linked cytoskeletal proteins [3]. 

Proteins of the cornified envelope 

The cornified envelope (CE) contains highly cross-linked 
proteins formed from special precursor proteins synthesized 
in the granular cell layer, particularly involucrin, loricrin, 
and cornifin. In addition to these major protein components, 
several other minor unique proteins are also cross-linked to 
the cornified envelope. These include proteins with specific 
functions such as calcium binding proteins, antimicrobial 
and immune functional proteins, proteins that provide 
structural integrity to SC by binding to lipids and desmo- 
somes, and protease inhibitors. The cross-linking is pro¬ 
moted by the enzyme transglutaminase which is detectable 
histochemically in the granular cell layer and lower seg¬ 
ments of the stratum corneum. The y-glutamyl link that 
results from transglutaminase activity is extremely chemi¬ 
cally resistant and this provides the cohesivity and resiliency 
to the SC. 

Lamellar granules and inter-corneocyte lipids 

Lamellar granules or bodies (LG or LB) are specialized lipid¬ 
carrying vesicles formed in suprabasal keratinocytes, des¬ 
tined for delivery of the lipids in the interface between the 
corneocytes. These lipids form the essential component of 
the epidermal permeability barrier and provide the "mortar" 
into which the corneocyte "bricks" are laid for the perme¬ 
ability barrier formation. When the granular keratinocytes 
mature to the SC, specific enzymes within the LB process 
the lipids, releasing the non-polar epidermal permeability 
barrier lipids, namely, cholesterol, free fatty acids and cera- 
mides, from their polar precursors - phospholipids, glucosyl 
ceramides, and cholesteryl sulfate, respectively. These 
enzymes include: lipases, phospholipases, sphingomyeli¬ 
nases, glucosyl ceramidases, and sterol sulfatases [4,3]. The 
lipids fuse together in the SC to form a continuous bi-layer. 
It is these lipids, along with the corneocytes, that constitute 
the bulk of the water barrier property of the SC [6,7]. 

Lipid-protein cross-links at the cornified envelope 

LG are enriched in a specific lipid unique to the keratinizing 
epithelia such as the human epidermis. This lipid (a cera- 
mide) has a very long chain omega-hydroxy fatty acid 
moiety with linoleic acid linked to the omega hydroxyl 
group in ester form. This lipid is processed within the SC to 
release the omega hydroxyl ceramide that becomes cross- 
linked to the amino groups of the cornified envelope pro¬ 


teins. The molecular structure of these components suggests 
that the glutamine and serine residues of CE envelope 
proteins such as loricrin and involucrin are covalently linked 
to the omega hydroxyl ceramides [8]. In addition, other 
free fatty acids (FFA) and ceramides (Cer), may also form 
protein cross-links on the extracellular side of the CE, pro¬ 
viding the scaffold for the corneocytes to the lipid membrane 
of the SC. 

Desmosomes and corneodesmosomes 

Desmosomes are specialized cell structures that provide cell¬ 
cell adhesion (Figure 1.1). They help to resist shearing forces 
and are present in simple and stratified squamous epithelia 
as in human epidermis. Desmosomes are molecular com¬ 
plexes of cell adhesion proteins and linking proteins that 
attach the cell surface adhesion proteins to intracellular 
keratin cytoskeletal filaments proteins. Some of the spe¬ 
cialized proteins present in desmosomes are cadherins, 
calcium binding proteins, desmogleins, and desmocollins. 
Cross-linking of other additional proteins such as envo- 
plakins and periplakins further stabilizes desmosomes. 
Corneodesmosomes are remnants of the desmosomal 
structures that provide the attachment sites between 
corneocytes and cohesiveness for the corneocytes in the SC. 
Corneodesmosomes have to be degraded by specialized 
proteases and glycosidases, mainly serine proteases, for the 
skin to shed in a process called desquamation [9]. 

Keratohyalin granules 

Keratohyalin granules are irregularly shaped granules 
present in the granular cells of the epidermis, thus providing 
these cells their granular appearance (Figure 1.1). These 
organelles contains abundant amount of keratins "bundled" 
together by a variety of other proteins, most important of 
which is filaggrin (filament aggregating protein). An impor¬ 
tant role of this protein, in addition to bundling of the major 
structural protein, keratin of the epidermis, is to provide the 
natural moisturizing factor (NMF) for the SC. Filaggrin con¬ 
tains all the amino acids that are present in the NMF. 
Filaggrin, under appropriate conditions, is dephosphorylated 
and proteolytically digested during the process when granu¬ 
lar cells mature into corneocytes. The amino acids from 
filaggrin are further converted to the NMF components by 
enzymatic processing and are retained inside the corneo¬ 
cytes as components of NMF [4,9]. 


Functions of epidermal barrier 

Water evaporation barrier (epidermal 
permeability barrier) 

Perhaps the most studied and the most important function 
of the SC is the formation of the epidermal permeability 
barrier [1,4,10]. The SC limits the transcutaneous movement 


5 



BASIC CONCEPTS Skin Physiology 


of water and electrolytes, a function that is essential for ter¬ 
restrial survival. Lipids, particularly ceramides, cholesterol, 
and FFA, together form lamellar membranes in the extracel¬ 
lular spaces of the SC which limit the loss of water and 
electrolytes. Corneocytes are embedded in this lipid-enriched 
matrix, and the cornified envelope, which surrounds cor¬ 
neocytes, provides a scaffold necessary for the organization 
of the lamellar membranes. Extensive research, mainly by 
Peter Elias' group has elucidated the structure, properties, 
and the regulation of the skin barrier by integrated mecha¬ 
nisms [5,7,11]. Barrier disruption triggers a cascade of 
biochemical processes leading to rapid repair of the epider¬ 
mal barrier. These steps include increased keratinocyte 
proliferation and differentiation, increased production of 
corneocytes, and production, processing, and secretion of 
barrier lipids, ultimately leading to the repair of the epider¬ 
mal permeability barrier. These events are described in 
more detail in the barrier homeostasis section below. A list 
of the different functions of human epidermis is shown in 
Table 1.2. 

Mechanical barrier 

Cornified envelope provides mechanical strength and rigid¬ 
ity to the epidermis, thereby protecting the host from injury. 
Specialized protein precursors and their modified amino acid 
cross-links provide the mechanical strength to the SC. 
One such protein, trichohyalin, is a multifunctional cross- 
bridging protein that forms intra- and inter-protein cross¬ 
links between cell envelope structure and cytoplasmic 
keratin filament network [12]. Special enzymes called trans¬ 


Table 1.2 Barrier functions of the epidermis. 

Function 

Localization/components involved 

Water and electrolyte 

SC/corneocyte proteins and 

permeability barrier 

extracellular lipids 

Mechanical barrier 

SC/corneocytes, cornified envelope 

Microbial barrier/immune 

function 

SC/lipid components/viable epidermis 

Hydration/moisturization 

SC/NMF 

Protection from 
environmental toxins/drugs 

SC/corneocytes, cornified envelope 

Desquamation 

SC, epidermis/proteases and 
glycosidases 

UV barrier 

SC/melanins of SC/epidermis 

Oxidative stress barrier 

SC, epidermis/antioxidants 


glutaminases, some present exclusively in the epidermis 
(transglutaminase 3), catalyze this cross-linking reaction. 
In addition, adjacent corneocytes are linked by corneo- 
desmosomes, and many of the lipids of the SC barrier 
are also chemically cross-linked to the cornified envelope. 
All these chemical links provide the mechanical strength 
and rigidity to the SC. 

Antimicrobial barrier and immune protection 

The epidermal barrier acts as a physical barrier to pathogenic 
organisms that attempt to penetrate the skin from the 
outside environment. Secretions such as sebum and sweat 
and their acid pH provide antimicrobial properties to skin. 
Innate immune function of keratinocytes and other immune 
cells of the epidermis such as Langerhans cells and phago¬ 
cytes provide additional immune protection in skin. 
Epidermis also generates a spectrum of antimicrobial lipids, 
peptides, nucleic acids, proteases, and chemical signals that 
together forms the antimicrobial barrier (Table 1.3). The 
antimicrobial peptides are comprised of highly conserved, 
small, cysteine rich, cationic proteins that are expressed in 
large amounts in skin. Desquamation, which causes the 
outward movement of corneocytes and their sloughing off 
at the surface, also serves as a built-in mechanism inhibiting 
pathogens from colonizing the skin. 

NMF and skin hydration and moisturization 

NMF is a collection of water-soluble compounds that are 
found in the stratum corneum (Table 1.4). These compounds 
compose approximately 20-30% of the dry weight of the 


Table 1.3 Antimicrobial components of epidermis and stratum 

corneum. 

Component 

Class of compound 

Localization 

Free fatty acids 

Lipid 

Stratum corneum 

Glucosyl ceramides 

Lipid 

Stratum corneum 

Ceramides 

Lipid 

Stratum corneum 

Sphingosine 

Lipid 

Stratum corneum 

Defensins 

Peptides 

Epidermis 

Cathelicidin 

Peptides 

Epidermis 

Psoriasin 

Protein 

Epidermis 

RNAse 7 

Nucleic acid 

Epidermis 

Low pH 

Protons 

Stratum corneum 

"Toll-like" receptors 

Protein signaling molecules 

Epidermis 

Proteases 

Proteins 

Stratum corneum 

and epidermis 


NMF, natural moisturizing factor; SC, stratum corneum. 


6 








1. Epidermal barrier 


Table 1.4 Approximate composition of skin natural moisturizing 
factor. 


Components 

Percentage levels 

Amino acids and their salts (over a dozen) 

30-40 

Pyrrolidine carboxylic acid sodium salt, 
urocanic acid, ornithine, citruline (derived 
from filaggrin hydrolysis products) 

7-12 

Urea 

5-7 

Glycerol 

4-5 

Glucosamine, creatinine, ammonia, uric acid 

1-2 

Cations (sodium, calcium, potassium) 

10-11 

Anions (phosphates, chlorides) 

6-7 

Lactate 

10-12 

Citrate, formate 

0.5-1.0 


corneocyte. Many of the components of NMF are derived 
from the hydrolysis of filaggrin, a histidine- and glutamine - 
rich basic protein of the keratohyalin granule. The SC hydra¬ 
tion level controls the protease that hydrolyzes filaggrin and 
histidase that converts histidine to urocanic acid. As NMF is 
water soluble and can easily be washed away from the SC, 
the lipid layer surrounding the corneocyte helps seal the 
corneocyte to prevent loss of NMF. 

In addition to preventing water loss from the organism, 
the SC also acts to provide hydration and moisturization to 
skin. NMF components absorb and hold water allowing the 
outermost layers of the SC to stay hydrated despite exposure 
to the harsh external environment. Glycerol, a major com¬ 
ponent of the NMF, is an important humectant present in 
skin which contributes skin hydration. Glycerol is produced 
locally within the SC by the hydrolysis of triglycerides by 
lipases, but also taken up into the epidermis from the circu¬ 
lation by specific receptors present in the epidermis called 
aquaporins [13]. Other humectants in the NMF include 
urea, sodium and potassium lactates, and pyrrolidine car¬ 
boxylic acid (PCA) [9]. 

Protection from environmental toxins and topical 
drug penetration 

The SC also has the important task of preventing toxic sub¬ 
stances and topically applied drugs from penetrating the 
skin. The SC acts as a protective wrap because of the highly 
resilient and cross-linked protein coat of the corneocytes and 
the lipid-enriched intercellular domains. Pharmacologists 
and topical or "transdermal" drug developers are interested 
in increasing SC permeation of drugs into the skin. The 
multiple route(s) of penetration of drugs into the skin can 
be via hair follicles, interfollicular sites, or by penetration 


through corneocytes and lipid bilayer membranes of the 
SC [10]. The molecular weight, solubility, and molecular 
configuration of the toxins and drugs greatly influence the 
rate of penetration. Different chemical compounds adopt 
different pathways for skin penetration. 

Desquamation and the role of proteolytic 
enzymes 

The process by which individual corneocytes are sloughed 
off from the top of the SC is called desquamation. Normal 
desquamation is required to maintain the homeostasis of the 
epidermis. Corneocyte to corneocyte cohesion is controlled 
by the intercellular lipids as well as the corneodesmosomes 
that bind the corneocytes together. The presence of special¬ 
ized proteolytic enzymes and glycosidases in the SC help in 
cleavage of desmosomal bonds resulting in release of corneo¬ 
cytes [9]. In addition, the SC also contains protease inhibitors 
that keep these proteases in check and the balance of pro¬ 
tease-protease inhibitors have a regulatory role in the control 
of the desquamatory process. The desquamatory process is 
also highly regulated by the epidermal barrier function. 

The SC contains three families of proteases (serine, 
cysteine, and aspartate proteases), including the epidermal- 
specific serine proteases (SP), kallikrein-5 (SC tryptic enzyme 
[SCTE]), and kallikrein-7 (SC chymotryptic enzyme), as well 
as at least two cysteine proteases, including the SC thiol 
protease (SCTP), and at least one aspartate protease, 
cathepsin D. All these proteases have specific roles in the 
desquamatory process at different layers of the epidermis. 

Melanin and the UV barrier 

Although melanin is not typically considered a functional 
component of the epidermal barrier, its role in the protec¬ 
tion of the skin from UV radiation is indisputable. Melanins 
are formed in specialized dendritic cells called melanocytes 
in the basal layers of the epidermis. The melanin produced 
is transferred into keratinocytes in the basal and spinous 
layers. There are two types of melanins, depending on the 
composition and the color. The darker eumelanin is most 
protective to UV than the lighter, high sulfur-containing 
pheomelanin. The keratinocytes carry the melanins through 
the granular layer and into the SC layer of the epidermis. 
The melanin "dust" present in the SC is structurally different 
from the organized melanin granules found in the viable 
deeper layers of the epidermis. The content and composition 
of melanins also change in SC depending on sun exposure 
and skin type of the individual. 

Solar UV radiation is very damaging to proteins, lipids, 
and nucleic acids and causes oxidative damage to these 
macromolecules. The SC absorbs some UV energy but it is 
the melanin particles inside the corneocytes that provide the 
most protection. Darker skin (higher eumelanin content) is 
significantly more resistant to the damaging effects of UV on 
DNA than lighter skin. In addition, UV-induced apoptosis 


7 





BASIC CONCEPTS Skin Physiology 


(cell death that results in removal of damaged cells) is 
significantly greater in darker skin. This combination of 
decreased DNA damage and more efficient removal of UV- 
damaged cells plays a critical part in the decreased photo - 
carcinogenesis seen in individuals with darker skin [14]. In 
addition to melanin, trans-urocanic acid (tUCA), a product 
of histidine deamination produced in the SC, also acts as 
an endogenous sunscreen and protects skin from UV 
damage. 

Oxidative stress barrier 

The SC has been recognized as the main cutaneous oxida¬ 
tion target of UV and other atmospheric oxidants such as 
pollutants and cigarette smoke. UVA radiation, in addition 
to damaging the DNA of fibroblasts, also indirectly causes 
oxidative stress damage of epidermal keratinocytes. The oxi¬ 
dation of lipids and carbonylation of proteins of the SC lead 
to disruption of epidermal barrier and poor skin condition 
[15]. In addition to its effects on SC, UV also initiates and 
activates a complex cascade of biochemical reactions within 
the epidermis, causing depletion of cellular antioxidants and 
antioxidant enzymes such as superoxide dismutase (SOD) 
and catalase. Acute and chronic exposure to UV has been 
associated with depletion of SOD and catalase in the skin of 
hairless mice [16]. This lack of antioxidant protection further 
causes DNA damage, formation of thymine dimers, activa¬ 
tion of proinflammatory cytokines and neuroendocrine 
mediators, leading to inflammation and free radical genera¬ 
tion [17]. Skin naturally uses antioxidants to protect itself 
from photodamage. UV depletes antioxidants from outer SC. 
A gradient in the antioxidant levels (alfa-tocopherol, vitamin 
C, glutathione, and urate) with the lowest concentrations in 
the outer layers and a steep increase in the deeper layers of 
the SC protects it from oxidative stress [18]. Depletion of 
antioxidant protection leads to UV-induced barrier abnor¬ 
malities. Topical application of antioxidants would support 
these physiologic mechanisms and restore a healthy skin 
barrier [19,20]. 


Regulation of barrier homeostasis 

The epidermal barrier is constantly challenged by environ¬ 
mental and physiologic factors. Because a fully functional 
epidermal barrier is required for terrestrial life to exist, 
barrier homeostasis is tightly regulated by a variety of 
mechanisms. 

Desquamation 

Integral components of the barrier, corneocytes, and the 
intercellular lipid bilayers are constantly synthesized and 
secreted by the keratinocytes during the process of terminal 
differentiation. The continuous renewal process is balanced 
by desquamation which removes individual corneocytes in 


a controlled manner by degradation of desmosomal con¬ 
stituent proteins by the SC proteases. The protease activities 
are under the control of protease inhibitors which are co- 
localized with the proteases within the SC. In addition, the 
activation cascade of the SC proteases is also controlled by 
the barrier requirement. Lipids and lipid precursors such as 
cholesterol sulfate also regulate desquamation by controlling 
the activities of the SC proteases [21]. 

Corneocyte maturation 

Terminal differentiation of keratinocytes to mature cor¬ 
neocytes is controlled by calcium, hormonal factors, and 
by desquamation. High calcium levels in the outer nucle¬ 
ated layers of epidermis stimulate specific protein synthesis 
and activate the enzymes that induce the formation of 
corneocytes. A variety of hormones and cytokines control 
keratinocyte terminal differentiation, thereby regulating 
barrier formation. Many of the regulators of these hor¬ 
mones are lipids or lipid intermediates which are synthe¬ 
sized by the epidermal keratinocytes for the barrier 
function, thereby exerting control of barrier homeostasis 
by affecting the corneocyte maturation. For example, the 
activators and/or ligands for the nuclear hormone recep¬ 
tors (e.g. peroxisome proliferation activator receptor [PPAR] 
and vitamin D receptor) that influence keratinocyte ter¬ 
minal differentiation are endogenous lipids synthesized by 
keratinocytes. 

Lipid synthesis 

Epidermal lipids, the integral components of the permeabil¬ 
ity barrier, are synthesized and secreted by the keratinoc¬ 
ytes in the stratum granulosum after processing and 
packaging into the LB. Epidermis is a very active site of 
lipid synthesis under basal conditions and especially under 
conditions when the barrier is disrupted. Epidermis syn¬ 
thesizes ceramides, cholesterol, and FFA (a major compo¬ 
nent of phospholipids and ceramides). These three lipid 
classes are required in equimolar distribution for proper 
barrier function. The synthesis, processing, and secretion 
of these lipid classes are under strict control by the perme¬ 
ability barrier requirements. For example, under conditions 
of barrier disruption, rapid and immediate secretion by 
already packaged LB occurs as well as transcriptional and 
translational increases in key enzymes required for new 
synthesis of these lipids to take place. In addition, many 
of the hormonal regulators of corneocyte maturation are 
lipids or lipid intermediates synthesized by the epidermis. 
SC lipid synthesis and lipid content are also altered with 
various skin conditions such as inflammation and winter 
xerosis [22,23]. 

Environmental and physiologic factors 

Barrier homeostasis is under control of environmental 
factors such as humidity variations. High humidity (increased 


8 



1. Epidermal barrier 


SC hydration) downregulates barrier competence (as 
assessed by barrier recovery after disruption) whereas low 
humidity enhances barrier homeostasis. Physiologic factors 
can also have influence on barrier function. High stress 
(chronic as well as acute) increases corticosteroid levels and 
causes disruption of barrier homeostasis. Conditions that 
cause skin inflammation can stimulate the secretion of 
inflammatory cytokines such as interleukins, induce epider¬ 
mal hyperplasia, cause impaired differentiation, and disrupt 
epidermal barrier functions. 

Hormones 

Barrier homeostasis and SC integrity, lipid synthesis is all 
under the control of different hormones, cytokines, and 
calcium. Nuclear hormone receptors for both well-known 
ligands, such as thyroid hormones, retinoic acid, and vitamin 
D, and "liporeceptors" whose ligands are endogenous lipids 
control barrier homeostasis. These liporeceptors include 
peroxisome proliferator activator receptor (PPAR alfa, beta, 
and gamma) and liver X receptor (LXR). The activators for 
these receptors are endogenous lipids and lipid intermedi¬ 
ates or metabolites such as certain FFA, leukotrienes, pros¬ 
tanoids, and oxygenated sterols. These hormones, mediated 
by their receptors, control barrier at the level of epidermal 
cell maturation (corneocyte formation), transcriptional reg¬ 
ulation of terminal differentiation proteins and enzymes 
required for lipid processing, lipid transport, and secretion 
into FB [5]. 

pH and calcium 

Outermost SC pH is maintained in the acidic range, typically 
in the range 4.5-5.0, by a variety of different mechanisms. 
This acidity is maintained by formation of FFA from phos¬ 
pholipids; sodium proton exchangers in the SC and by the 
conversion of histidine of the NMF to urocanic acid by histi- 
dase enzyme in the SC. In addition, lactic acid, a major 
component of the NMF, has a major role in maintaining the 
acid pH of the SC. Maintenance of an acidic pH in the SC is 
important for the integrity and cohesion of the SC as well 
as the maintenance of the normal skin microflora. The 
growth of normal skin microflora is supported by acidic pH 
while a more neutral pH supports pathogenic microbes' 
invasion of the skin. 

This acidic pH is optimal for processing of precursor 
lipids to mature barrier forming lipids and for initiating the 
desquamatory process. The desquamatory proteases present 
in the outer SC such as the thiol proteases and cathepsins 
are more active in the acidic pH, whereas the SCCE and 
SCTE present in the lower SC are more active at neutral pH. 
When the pH gradient is disrupted, desquamation is 
decreased resulting in dry scaly skin and disrupted barrier 
function. 

In the normal epidermis, there is a characteristic intra- 
epidermal calcium gradient, with peak concentrations of 


calcium in the granular layer and decreasing all the way up 
to the SC [24]. The calcium gradient regulates barrier prop¬ 
erties by controlling the maturation of the corneocytes, 
regulating the enzymes that process lipids and by modulat¬ 
ing the desquamatory process. Calcium stimulates a variety 
of processes including the formation and secretion of FB, 
differentiation of keratinocytes, formation of cornified enve¬ 
lope precursor proteins, and cross-linking of these proteins 
by the calcium inducible enzyme transglutaminase. 
Specifically, high levels of calcium stimulate the expression 
of proteins required for keratinocyte differentiation, includ¬ 
ing key structural proteins of the cornified envelope, such 
as loricrin, involucrin, and the enzyme, transglutaminase 1, 
which catalyzes the cross-linking of these proteins into a 
rigid structure. 

Coordinated regulation of multiple 
barrier functions 

Co-localization of many of the barrier functions allows 
regulation of the functions of the epidermal barrier to be 
coordinated. For example, epidermal permeability barrier, 
antimicrobial barrier, mechanical protective barrier, and UV 
barrier are all co-localized in the SC. A disruption of one 
function can lead to multiple barrier disruptions, and there¬ 
fore multiple barrier functions are coordinately regulated 
[5]. Disruption of the permeability barrier leads to activation 
of the cytokine cascade (increased levels of primary 
cytokines, interleukin-1, and tumor necrosis factor-alfa) 
which in turn activates the synthesis of antimicrobial pep¬ 
tides of the SC. Additionally, the cytokines and growth 
factors released during barrier disruption lead to corneocyte 
maturation, thereby strengthening the mechanical and pro¬ 
tective barrier of the skin. Hydration of the skin itself con¬ 
trols barrier function by regulating the activities of the 
desquamatory proteases (high humidity decreases barrier 
function and stimulates desquamation). In addition, humid¬ 
ity levels control filaggrin hydrolysis which releases the free 
amino acids that form the NMF (histidine, glutamine 
arginine, and their by-products) and trans-urocanic acid 
(deamination of histidine) which serves as a UV barrier. 


Methods for studying barrier structure 
and function 

Physical methods 

SC integrity and desquamation can be measured using tape 
stripping methods. Under dry skin conditions, when the 
barrier is compromised, corneocytes do not separate singly 
but as "clumps." This can be quantified by using special tapes 
and visualizing the corneocytes removed by light micros¬ 
copy. Another harsher tape-stripping method involves strip¬ 
ping of the SC using cyanoacrylate glue. These physical 
methods provide a clue to the binding forces that hold the 


9 



BASIC CONCEPTS Skin Physiology 


corneocyte together. The efficacy of treatment with skin 
moisturizers or emollients that improve skin hydration and 
reduce scaling can be quantitated using these methods. 

Instrumental methods 

The flux of water vapor through the skin (transepidermal 
water loss [TEWL]) can be determined using an 
evaporimeter [25]. This instrument contains two water 
sensors mounted vertically in a chamber one above the 
other. When placed on the skin in a stable ambient environ¬ 
ment the difference in water vapor values between the two 
sensors is a measure of the flow of water coming from the 
skin (TEWL). There are several commercially available evap- 
orimeters (e.g. Tewameter® [Courage & Khazaka, Koln, 
Germany]), which are widely used in clinical practice as well 
as in investigative skin biology. Recovery of the epidermal 
barrier (TEWL) after disruption using physical methods (e.g. 
tape strips) or chemical methods (organic solvent washing) 
provides valuable information on epidermal barrier proper¬ 
ties [26]. 

Skin hydration can be measured using the Corneometer® 
(Courage & Khazaka, Koln, Germany). The measurement is 
based on capacitance of a dielectric medium. Any change in 
the dielectric constant caused by skin surface hydration vari¬ 
ation alters the capacitance of a precision measuring capaci¬ 
tor. The measurement can detect even the slightest changes 
in hydration level. Another important recent development 
in skin capacitance methodology is the SkinChip® (L'Oreal, 
Paris, France). Skin capacitance imaging of skin surface can 
be obtained using the SkinChip. This method provides infor¬ 
mation on skin microrelief, level of SC hydration, and sweat 
gland activity. SkinChip technology can be used to quantify 
regional variation in skin, skin changes with age, effects of 
hydrating formulations, surfactant effects on corneocytes, 
acne, and skin pore characteristics [27]. 

Several other recently developed methods for measuring 
epidermal thickness such as confocal microscopy, dermatoe- 
chography, and dermatoscopy can provide valuable infor¬ 
mation on skin morphology and barrier abnormalities [28]. 
Other more sophisticated (although not easily portable) 
instrumentation techniques such as ultrasound, optical 
coherence tomography, and magnetic resonance imaging 
(MRI) can provide useful information on internal structures 
of SC and/or epidermis and its improvements with treat¬ 
ment. MRI has been successfully used to evaluate skin 
hydration and water behavior in aging skin [29]. 

Biologic methods 

Ultrastructural details of SC and the intercellular spaces of 
the SC can be visualized using transmission electron micro¬ 
scopy of thin vertical sections and freeze-fracture replicas, 
field emission scanning electron microscopy, and immun¬ 
ofluorescence confocal laser scanning microscopy [30]. The 
ultrastructural details of the lipid bi-layers within the SC can 


be visualized by electron microscopy after fixation using 
ruthenium tetroxide. The existence of corneodesmosomes 
in the SC, and their importance in desquamation, can be 
measured by scanning electron microscopy of skin surface 
replicas. 

The constituent cells of the SC, the corneocytes, can be 
visualized and quantitated by scraping the skin surface or by 
use of a detergent solution. The suspension so obtained can 
be analyzed by microscopy, biochemical or immunologic 
techniques. 

Punch or shaved biopsy techniques can be combined with 
immunohistochemistry using specific SC and/or epidermis 
specific antibodies to quantify the SC quality. Specific anti¬ 
bodies for keratinocyte differentiation specific proteins, 
desmosomal proteins, or specific proteases can provide 
information on skin barrier properties. 


Relevance of skin barrier to cosmetic 
product development 

Topical products that influence barrier functions 

The human skin is constantly exposed to a hostile 
environment: changes in relative humidity, extremes of 
temperature, environmental toxins, and daily topically 
applied products. Daily exposure to soaps and other 
household chemicals can compromise skin barrier properties 
and cause unhealthy skin conditions. Prolonged exposure to 
surfactants removes the epidermal barrier lipids and 
enhances desquamation leading to impaired barrier proper¬ 
ties [4,10]. Allergic reactions to topical products can 
result in allergic or irritant contact dermatitis, resulting in 
itchy and scaly skin and skin redness leading to barrier 
perturbations. 

Cosmetics that restore skin barrier properties 

Water is the most important plasticizer of SC. Cracking and 
Assuring of skin develops as SC hydration declines below a 
critical threshold. Skin moisturization is a property of the 
outer SC (also known as stratum disjunctum) as corneocytes 
of the lower SC (stratum compactum) are hydrated by the 
body fluids. "Moisturizers" are substances that when applied 
to skin add water and/or retains water in the SC. The NMF 
components present in the outer SC act as humectants, 
absorb moisture from the atmosphere, and are sensitive to 
humidity of the atmosphere. The amino acids and their 
metabolites, along with other inorganic and organic osmo- 
lytes such as urea, lactic acid, taurine, and glycerol act as 
humectants within the outer SC. Secretions from sebaceous 
glands on the surface of the skin also act as emollients and 
contribute to skin hydration. A lack of any of these compo¬ 
nents can contribute to dry scaly skin. Topical application of 
all of the above components can act as humectants, and can 
relieve dry skin condition and improve skin moisturization 


10 



1. Epidermal barrier 


and barrier properties. Film-forming polysaccharide materi¬ 
als such as hyaluronic acid binds and retains water and helps 
to keep skin supple and soft. 

In addition to humectants, emollients such as petroleum 
jelly, hydrocarbon oils and waxes, mineral and silicone oils, 
and paraffin wax provide an occlusive barrier to the skin, 
preventing excessive moisture loss from the skin surface. 

Topically applied barrier compatible lipids also contribute 
to skin moisturization and improved skin conditions. 
Chronologically aged skin exhibits delayed recovery rates 
after defined barrier insults, with decreased epidermal lipid 
synthesis. Application of a mixture of cholesterol, ceramides, 
and essential/non-essential FFAs in an equimolar ratio was 
shown to lead to normal barrier recovery, and a 3:1:1:1 
ratio of these four ingredients demonstrated accelerated 
barrier recovery [31]. 

Topical application of antioxidants and anti-inflammatory 
agents also protects skin from UV-induced skin damage by 
providing protection from oxidative damage to skin proteins 
and lipids [19,20]. 

Skin irritation from cosmetics 

Thousands of ingredients are used by the cosmetic industry. 
These include pure compounds, mixtures, plant extracts, oils 
and waxes, surfactants, detergents, preservatives, and poly¬ 
mers. Although all the ingredients used by the cosmetic 
industry are tested for safety, some consumers may still 
experience reactions to some of them. Most common reac¬ 
tions are irritant contact reactions while allergic contact 
reactions are less common. Irritant reactions tend to be more 
rapid and cause mild discomfort and redness and scaling 
of skin. Allergic reactions can be delayed, more persistent, 
and sometimes severe. Ingredients previously considered 
safe can be irritating in a different formulation because of 
increased penetration into skin. More than 30% of the 
general population perceives their skin as sensitive. It is 
believed that the perception of sensitive skin is, at least in 
part, related to skin barrier function. People with impaired 
barrier function may experience higher irritation to a par¬ 
ticular ingredient because of its increased penetration into 
deeper layers of the skin. 


Conclusions and future trends 

Major advances have been made in the last several decades 
in understanding the complexity and functions of the SC. 
Extensive research by several groups has elucidated the 
metabolically active role of SC and characterized the major 
components within it and their importance in providing 
protection from the external environment. New insights 
into the molecular control mechanisms of desquamation, 
lipid processing, barrier function, and antimicrobial protec¬ 
tion have been elucidated in the last decade. 


Knowledge of other less well-known epithelial organelles 
such as intercellular junctions, tight junctions, and gap junc¬ 
tions and their role in barrier function in the skin is being 
elucidated. Intermolecular links that connect intercellular 
lipids with the corneocytes of the SC and their crucial role 
for maintaining barrier function is an area being actively 
researched. 

New knowledge of the corneocyte envelope structure 
and the physical state of the intercellular lipid crystallinity 
and their interrelationship would lead to development of 
new lipid actives for improving SC moisturization and for 
treatment of skin barrier disorders. Further research in the 
cellular signaling events that control the communication 
between SC and the viable epidermis will shed more light 
on barrier homeostasis mechanisms. 

Novel delivery systems have an increasingly important 
role in the development of effective skin care products. 
Delivery technologies such as lipid systems, nanoparticles, 
microcapsules, polymers, and films are being pursued not 
only as vehicles for delivering cosmetic actives through skin, 
but also for improving barrier properties of the skin. 

Undoubtedly, skin care and cosmetic companies will 
exploit this new knowledge in developing novel and more 
efficacious products for strengthening the epidermal barrier 
and to improve and enhance the functional and aesthetic 
properties of the human skin. 

References 

1 Elias PM. (1983) Epidermal lipids, barrier function, and desqua¬ 
mation. J Invest Dermatol 80, 44s-9s. 

2 Menon GK, Feingold KR, Elias PM. (1992) Lamellar body 
secretory response to barrier disruption. J Invest Dermatol 98, 
279-89. 

3 Downing DT. (1992) Lipid and protein structures in the perme¬ 
ability barrier of mammalian epidermis. J Lipid Res 33, 301-13. 

4 Rawlings AV, Matts PJ. (2005) Stratum corneum moisturization 
at the molecular level: an update in relation to the dry skin cycle. 
J Invest Dermatol 124, 1099-11. 

5 Elias PM. (2005) Stratum corneum defensive functions: an inte¬ 
grated view. J Invest Dermatol 125, 183-200. 

6 Elias PM. (1996) Stratum corneum architecture, metabolic 
activity and interactivity with subjacent cell layers. Exp Dermatol 
5, 191-201. 

7 Elias PM, Feingold KR. (1992) Lipids and the epidermal water 
barrier: metabolism, regulation, and pathophysiology. Semin 
Dermatol 11, 176-82. 

8 Uchida Y, Holleran WM. (2008) Omega-O-acylceramide, a lipid 
essential for mammalian survival. J Dermatol Sci 51, 77-87. 

9 Harding CR, Watkinson A, Rawlings AV, Scott IR. (2000) Dry 
skin, moisturization and corneodesmolysis. Int J Cosmet Sci 22, 
21-52. 

10 Schaefer H, Redelmeier TE, eds. (1996) Skin Barrier: Principles of 
Percutaneous Absorption. Karger, Basel. 

11 Elias PM, Menon GK. (1991) Structural and lipid biochemical 
correlates of the epidermal permeability barrier. Adv Lipid Res 24, 
1-26. 


11 



BASIC CONCEPTS Skin Physiology 


12 Steinert PM, Parry DA, Marekov LN. (2003) Trichohyalin 
mechanically strengthens the hair follicle: multiple cross- 
bridging roles in the inner root shealth. J Biol Chem 278, 
41409-19. 

13 Choi EH, Man M-Q, Wang F, Zhang X, Brown BE, Feingold KR, 
et al. (2005) Is endogenous glycerol a determinant of stratum 
corneum hydration in humans? J Invest Dermatol 125, 288-93. 

14 Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller 
SA, Tadokoro T, et al. (2006) Human skin responses to UV radia¬ 
tion: pigment in the upper epidermis protects against DNA 
damage in the lower epidermis and facilitates apoptosis. FASEB 
J 20, 1486-8. 

15 Sander CS, Chang H, Salzmann S, Muller CSL, Ekanayake- 
Mudiyanselage S, Eisner P, et al. (2002) Photoaging is associated 
with protein oxidation in human skin in vivo. J Invest Dermatol 
118, 618-25. 

16 Pence BC, Naylor MF. (1990) Effects of single-dose UV radiation 
on skin SOD, catalase and xanthine oxidase in hairless mice. 
J Invest Dermatol 95, 213-6. 

17 Pillai S, Oresajo C, Hayward J. (2005) UV radiation and skin 
aging: roles of reactive oxygen species, inflammation and pro¬ 
tease activation, and strategies for prevention of inflammation- 
induced matrix degradation. Int J Cosmet Sci 27, 17-34. 

18 Weber SU, Thiele JJ, Cross CE, Packer L. (1999) Vitamin C, uric 
acid, and glutathione gradients in murine stratum corneum and 
their susceptibility to ozone exposure. J Invest Dermatol 113, 
1128-32. 

19 Lopez-Torres M, Thiele JJ, Shindo Y, Han D, Packer L. (1998) 
Topical application of alpha-tocopherol modulates the antioxi¬ 
dant network and diminishes UV-induced oxidative damage in 
murine skin. Br J Dermatol 138, 207-15. 

20 Pinnell SR. (2003) Cutaneous photodamage, oxidative stress, 
and topical antioxidant protection. J Am Acad Dermatol 48, 
1-19. 


21 Madison KC. (2003) Barrier function of the skin: "la raison 
d'etre" of the epidermis. J Invest Dermatol 121, 231-41. 

22 Chatenay F, Corcuff P, Saint-Leger D, Leveque JL. (1990) 
Alterations in the composition of human stratum corneum lipids 
induced by inflammation. Photodermatol Photoimmunol Photomed 
7, 119-22. 

23 Saint-Leger D, Francois AM, Leveque JL, Stoudemayer TJ, 
Kligman AM, Grove G. (1999) Stratum corneum lipids in skin 
xerosis. Dermatologica 178, 151-5. 

24 Menon GK, Grayson S, Elias PM. (1985) Ionic calcium reservoirs 
in mammalian epidermis: ultrastructural localization by ion- 
capture cytochemistry. J Invest Dermatol 84, 508-12. 

25 Nilsson GE. (1977) Measurement of water exchange through 
the skin. Med Biol Eng Comput 15, 209. 

26 Pinnagoda J, Tupker RA. (1995) Measurement of the transepi- 
dermal water loss. In: Serup J, Jemec GBE, eds. Handbook of 
Non-Invasive Methods and the Skin. Boca Raton, FL: CRC Press, 
pp. 173-8. 

27 Leveque JL, Querleux B. (2003) SkinChip, a new tool 
for investigating the skin surface in vivo. Skin Res Technol 9, 
343-7. 

28 Corcuff P, Gonnord G, Pierard GE, Leveque JL. (1996) In vivo 
confocal microsocopy of human skin: a new design for cosmetol¬ 
ogy and dermatology. Scanning 18, 351-5. 

29 Richard S, Querleux B, Bittoun J, Jolivet O, Idy-Peretti I, de 
Lacharriere O, et al. (1993) Characterization of skin in vivo by 
high resolution magnetic resonance imaging: water behavior 
and age-related effects. J Invest Dermatol 100, 705-9. 

30 Corcuff P, Fiat F, Minondo AM. (2001) Ultrastructure of human 
stratum coreum. Skin Pharmacol Appl Skin Physiol 1, 4-9. 

31 Zettersten EM, Ghadially R, Feingold KR, Crumrine D, Elias PM. 
(1997) Optimal ratios of topical stratum corneum lipids improve 
barrier recovery in chronologically aged skin. J Am Acad Dermatol 
37, 403-8. 


12 


Chapter 2: Photoaging 

Murad Alam and Jillian Havey 

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 


BASIC CONCEPTS 

• UV radiation damages human skin connective tissue through several interdependent, but distinct, processes. 

• The normal dermal matrix is maintained through signaling transduction pathways, transcription factors, cell surface receptors, 
and enzymatic reactions. 

• UV radiation produces reactive oxygen species which inhibit procollagen production, degrade collagen, and damage fibroblasts. 


Introduction 

Skin, the largest human organ, is chronically exposed to UV 
radiation from the sun. Thinning of the ozone layer, which 
increases UV transmittance to the Earth, has heightened 
awareness of the potential injurious skin effects of exposure 
to UV radiation: photoaging, sunburn, immunosuppression, 
and carcinogenesis. Photoaging, the most common form of 
skin damage caused by UV exposure, produces damage to 
connective tissue, melanocytes, and the microvasculture [i]. 
Recent advances in understanding photoaging in human 
skin have identified the physical manifestations, histologic 
characteristics, and molecular mechanisms of UV 
exposure. 


Definition 

Photoaging is the leading form of skin damage caused by 
sun exposure, occurring more frequently than skin cancer. 
Chronic UV exposure results in premature skin aging, 
termed cutaneous photoaging, which is marked by fine and 
coarse wrinkling of the skin, dyspigmentation, sallow color, 
textural changes, loss of elasticity, and premalignant actinic 
keratoses. Most of these clinical signs are caused by dermal 
alterations. Pigmentary disorders such as seborrheic kera¬ 
toses, lentigines, and diffuse hyperpigmentation are charac¬ 
teristic of epidermal changes [2]. 

These physical characteristics are confirmed histologically 
by epidermal thinning and disorganization of the dermal 
connective tissue (see p. i4). Loss of connective tissue inter- 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


stitial collagen fibrils and accumulation of disorganized con¬ 
nective tissue elastin leads to solar elastosis, a condition 
characteristic of photoaged skin [3]. Similar alterations in 
the cellular component and the extracellular matrix of the 
connective tissue of photoaged skin may affect superficial 
capillaries, causing surface telangiectasias [4]. 


Physiology 

Photoaged versus chronically aged skin 

Skin, like all other organs, ages over time. Aging can be 
defined as intrinsic and extrinsic. Intrinsic aging is a hall¬ 
mark of human chronologic aging and occurs in both sun- 
exposed and non-sun-exposed skin. Extrinsic aging, on the 
contrary, is affected by exposure to environmental factors 
such as UV radiation. While sun-protected chronically aged 
skin and photoaged chronically aged skin share common 
characteristics, many of the physical characteristics of skin 
that decline with age show an accelerated decline with 
photoaging [3]. Compared with photodamaged skin, sun- 
protected skin is characterized by dryness, fine wrinkles, 
skin atrophy, homogeneous pigmentation, and seborrheic 
keratoses [6]. Extrinsically aged skin, on the contrary, is 
characterized by roughness, dryness, both fine and coarse 
wrinkles, atrophy, uneven pigmentation, and superficial 
vascular abnormalities (e.g. telangiectasias) [6]. It is impor¬ 
tant to note that these attributes are not absolute and can 
vary according to Fitzpatrick skin type classification and 
history of sun exposure. 

While the pathophysiology of photoaged and photo- 
protected skin differ, the histologic features of these two 
entities are distinct. In photo-protected skin, a thin epider¬ 
mis is present with an intact stratum corneum, the der- 
moepidermal junction and the dermis are flattened, and 
dermal fibroblasts produce less collagen. In photoaged skin, 


13 








BASIC CONCEPTS Skin Physiology 


the thickness of the epidermis can either increase or decrease, 
corresponding to areas of keratinocyte atypia. The dermoep- 
idermal junction is atrophied in appearance and the basal 
membrane thickness is increased, reflecting basal keratino¬ 
cyte damage. 

Changes in the dermis of photoaged skin can vary based 
on the amount of acquired UV damage. Solar elastosis is the 
most prominent histologic feature of photoaged skin. The 
quantity of elastin in the dermis decreases in chronically 
aged skin, but in UV-exposed skin, elastin increases in pro¬ 
portion to the amount of UV exposure [7,8]. Accumulated 
elastic fibers occupy areas in the dermal compartment previ¬ 
ously inhabited by collagen fibers [9]. This altered elastin 
deposition is manifest clinically as wrinkles and yellow dis¬ 
coloration of the skin. 

Another feature of photoaged skin is collagen fibril disor¬ 
ganization. Mature collagen fibers, which constitute the 
bulk of the skin's connective tissue, are degenerated and 
replaced by collagen with a basophilic appearance, termed 
basophilic degeneration. Additional photoaged skin charac¬ 
teristics include an increase in the deposition of gly- 
cosaminoglycans and dermal extracellular matrix proteins 
[10,11]. In fact, the overall cell population in photodam- 
aged skin increases, leading to hyperplastic fibroblast 
proliferation and infiltration of inflammatory substrates 
that cause chronic inflammation (heliodermatitis) [12]. 
Changes in the microvasculature also occur, as is clinically 
manifested in surface telangiectasias and other vascular 
abnormalities. 


Photobiology 

In order to fully understand the molecular mechanisms 
responsible for photoaging in human skin, an awareness of 
the UV spectrum is crucial. The UV spectrum is divided into 
three main components: UVC (270-290nm), UVB (290- 
320nm), and UVA (320-400nm). While UVC radiation is 
filtered by ozone and atmospheric moisture, and conse¬ 
quently never reaches the Earth, UVA and UVB rays do 
reach the terrestrial surface. Although the ratio of UVA to 
UVB rays is 20:1 [13] and UVB is greatest during the 
summer months, both forms of radiation have acute and 
chronic effects on human skin. 

Photoaging is the superposition of UVA and UVB radiation 
on intrinsic aging. In order to exert biologic effects on human 
skin, both categories of UV rays must be absorbed by 
chromophores in the skin. Depending on the wavelength 
absorbed, UV light interacts with different skin cells at dif¬ 
ferent depths (Figure 2.1). More specifically, energy from 
UVB rays is mostly absorbed by the epidermis and affects 
epidermal cells such as the keratinocytes, whereas energy 
from UVA rays affects both epidermal keratinocytes and the 
deeper dermal fibroblasts. The absorbed energy is converted 
into varying chemical reactions that cause histologic and 
clinical changes in the skin. UVA absorption by chromo¬ 
phores mostly acts indirectly by transferring energy to 
oxygen to generate reactive oxygen species (ROS), which 
subsequently causes several effects such as transcription 
factor activation, lipid peroxidation, and DNA-strand breaks. 
On the contrary, UVB has a more direct effect on the absorb- 


UV-B 


UV-A 



Figure 2.1 Ultraviolet light interacts with 
different skin cells at different depths. More 
specifically, energy from UVB rays is mostly 
absorbed by the epidermis and affects 
epidermal cells such as the keratinocytes. 
Energy from UVA rays affects both epidermal 
keratinocytes and the deeper dermal 
fibroblasts. AP-1, activator protein 1; 

NF-kB, nuclear factor kB; MMP, matrix 
metalloproteinase; mtDNA, mitochondrial 
DNA; ROS, reactive oxygen species. 
(Reproduced by permission of: Blackwell 
Publishing. This figure was published in: 
Berneburg M, Plettenberg H, Krutmann J. 
(2000) Photoaging in human skin. 
Photodermatol Photoimmunol Photomed 
16, figure 1, p. 240.) 


14 





2. Photoaging 


ing chromophores and causes cross-linking of adjacent 
DNA pyrimidines and other DNA-related damage [14]. 
Approximately 50% of UV-induced photodamage is from 
the formation of free radicals, while mechanisms such as 
direct cellular injury account for the remainder of UV effects 
[15]. 

Cutaneous microvasculature 

Intrinsically aged skin and photodamaged skin share similar 
cutaneous vasculature characteristics, such as decreased 
cutaneous temperature, pallor, decreased cutaneous vessel 
size, reduced erythema, reduced cutaneous nutritional 
supply, and reduced cutaneous vascular responsiveness [16- 
18]. However, there are also significant differences in the 
microvasculature of chronologic sun-protected versus pho¬ 
toaged skin. Studies have reported that the blood vessels in 
photoaged skin are obliterated and the overall horizontal 
architecture of the vascular plexuses is disrupted [19]. In 
contrast to photodamaged skin, intrinsically aged skin does 
not display a greatly disturbed pattern of horizontal vascu¬ 
lature. Additionally, while cutaneous vessel size has been 
reported to decrease with age in both scenarios, only photo¬ 
aged skin exhibits a large reduction in the number of dermal 
vessels. This reduction is especially highlighted in the upper 
dermal connective tissue, where it is hypothesized that 
chronic UV-induced degradation of elastic and collagen 
fibers is no longer able to provide the physical support 
required for normal cutaneous vessel maintenance [16]. 

Furthermore, preliminary studies have reported that the 
effects of exposure to acute UV radiation differ from chronic 
exposure. Recent studies have implied that a single exposure 
to UVB radiation induces skin angiogenesis in human skin 
in vivo [20,21]. The epidermis-derived vascular endothelial 
growth factor (VEGF) is an angiogenic factor that is signifi¬ 
cantly upregulated with UV exposure in keratinocytes in 
vitro and in human skin in vivo. Chung and Eun [16] have 
demonstrated that, compared to low VEGF expression in 
non-UV-irradiated control skin, epidermal VEGF expression 
increased significantly on days 2 and 3 post-UV-irradiation, 
consequently inducing cutaneous angiogenesis. Therefore, 
acute UV exposure has been shown to induce angiogenesis. 
However, chronic UV-exposed photodamaged skin exhibits 
a significant reduction in the number of cutaneous blood 
vessels. The reasons for this discrepancy between the effects 
of acute and chronic UV exposure on angiogenesis in vivo 
are still under investigation. 


Molecular mechanisms of photoaging 

During the last few years substantial progress has been made 
in exposing the molecular mechanisms accountable for pho¬ 
toaging in human skin. One major theoretical advance that 
has been elucidated by this work is that UV irradiation 


damages human skin by at least two interdependent 
mechanisms: 

1 Photochemical generation of ROS; and 

2 Activation of cutaneous signal transduction pathways. 
These molecular processes and their underlying components 
are described in detail below. Before these processes are 
highlighted, however, the structure and function of collagen 
must be understood. 

Collagen 

Type I collagen accounts for greater than 90% of the protein 
in the human skin, with type III collagen accounting for a 
smaller fraction (10%). The unique physical characteristics 
of collagen fibers are essential for providing strength, struc¬ 
tural integrity, and resilience to the skin. Dermal fibroblasts 
synthesize individual collagen polypeptide chains as precur¬ 
sor molecules called procollagen. These procollagen building 
blocks are assembled into larger collagen fibers through 
enzymatic cross-linking and form the three-dimensional 
dermal network mainly made of collagen types I and III. This 
intermolecular covalant cross-linking step is essential for 
maintenance and structural integrity of large collagen fibers, 
especially type I collagen. 

Natural breakdown of type I collagen is a slow process and 
occurs through enzymatic degradation [22]. Dermal colla¬ 
gen has a half-life of greater than 1 year [22], and this slow 
rate of type I collagen turnover allows for disorganization 
and fragmentation of collagen which impair its functions. In 
fact, fragmentation and dispersion of collagen fibers is a 
feature of photodamaged skin that is clinically manifest in 
the changes associated with photodamaged human skin. 

The regulation of collagen production is an important 
mechanism to understand before discussing how this process 
is impaired. In general, collagen gene expression is regulated 
by the cytokine, transforming growth factor (3 (TGF-(3), and 
the transcription factor, activator protein (AP-1), in human 
skin fibroblasts. When TGF-(3s bind to their cell surface 
receptors (TpRI and TpRII), transcription factors Smad2 and 
Smad3 are activated, combine with Smad4, and enter the 
nucleus, where they regulate type I procollagen production. 
AP-1 has an opposing effect and inhibits collagen gene tran¬ 
scription by either direct suppression of gene transcription 
or obstructing the Smad complex from binding to the TGF-P 
target gene (Figure 2.2) [23]. Therefore, in the absence of 
any inhibiting factors, the TGF-p/Smad signaling pathway 
results in a net increase in procollagen production. 

How does UV irradiation stimulate photoaging? 

UV irradiation stimulates photoaging through several mole¬ 
cular mechanisms, discussed in detail below. 

Reactive oxygen species 

Approximately 50% of UV-induced photodamage is from 
the formation of free radicals, while mechanisms such as 


15 



BASIC CONCEPTS Skin Physiology 


TGF-p 



Figure 2.2 The regulation of procollagen production: the TGF-|3/Smad 
signaling pathway. AP-1, activator protein 1; T|3R, TGF-J3 receptor; TGF-J3, 
transforming growth factor |3. (Reproduced by permission of: Elsevier Ltd. 
This figure was published in: Kang S, Fisher G, Voorhees JJ. (2001) 
Photoaging pathogenesis, prevention, and treatment. Clin Geriatric Med 
17(4), figure 1, p. 645.) 

direct cellular injury account for the remainder of UV effects 
[15]. Proposed in 1954, the free radical theory of aging sug¬ 
gests that aging is a result of reactions caused by excessive 
amounts of free radicals, which contain one or more 
unpaired electrons [24]. Generation of ROS occurs during 
normal chronologic aging and when human skin is exposed 
to UV light in photoaging [25]. ROS mediate deleterious 
post-translational effects on aging skin through direct chem¬ 
ical modifications to mitochondrial DNA (mtDNA), cell 
lipids, deoxyribonucleic acids (DNA), and dermal matrix 
proteins, including collagens. In fact, a 4977 base-pair dele¬ 
tion of mtDNA was recently found in dermal human fibrob¬ 
last cells. This deletion is induced by UVA via ROS and is a 
marker of UVA photodamage [26]. 

UV radiation inhibits procollagen production: 
TGF-p/Smad signaling pathway 

UV light inhibits procollagen production through two signal¬ 
ing pathways: downregulation of TPRII and inhibition of 
target gene transcription by AP-1. UV radiation has been 
reported to disrupt the skin collagen matrix through the 
TGF-p/Smad pathway [1]. More specifically, UV radiation 
downregulates the TGF-p type II receptor (TpRII) and results 
in a 90% reduction of TGF-p cell surface binding, conse¬ 
quently reducing downstream activation of the Smad 2, 3, 
4 complex and type I procollagen transcription. 

Additionally, UV radiation activates AP-1, which binds 
factors that are part of the procollagen type I transcriptional 


complex. This, in turn, reduces TGF-p target gene expres¬ 
sion, such as expression of type I procollagen [27]. 

UV-induced matrix metalloproteinases stimulate 
collagen degradation 

It has been demonstrated that UV irradiation affects the 
post-translational modification of dermal matrix proteins 
(through ROS) and also downregulates the transcription of 
these same proteins (through the TGF-p/Smad signaling 
pathway). UVA and UVB light also induces a wide variety 
of matrix metalloproteinases (MMPs) [28]. As their name 
suggests, MMPs degrade dermal matrix proteins, specifically 
collagens, through enzymatic activity. UV-induced MMP-1 
initiates cleavage of type I and III dermal collagen, followed 
by further degradation by MMP-3 and MMP-9. 

Recall that type I collagen fibrils are stabilized by covalent 
cross-links. When undergoing degradation by MMPs, col¬ 
lagen molecules can remain cross-linked within the dermal 
collagen matrix, thereby impairing the structural integrity of 
the dermis. In the absence of perfect repair mechanisms, 
MMP-mediated collagen damage can accrue with each UV 
exposure. This type of collective damage to the dermal 
matrix collagen is hypothesized to have a direct effect on the 
physical characteristics of photodamaged skin [14]. 

In addition to UV induction of MMPs, transcription factors 
may cause MMP activation. It has been reported that within 
hours of UV exposure, the transcription factors AP-1 and 
NF-kB are activated which, in turn, stimulate transcription 
of MMPs (Figure 2.3) [29]. 

Fibroblasts regulate their own collagen synthesis 

Fibroblasts have evolved to regulate their output of extra¬ 
cellular matrix proteins (including collagen) based on 
internal mechanical tension [30]. Type I collagen fibrils in 
the dermis serve as mechanical stabilizers and attachment 
sites for fibroblasts in sun-protected skin. Surface integrins 
on the fibroblasts attach to collagen and internal actin- 
myosin microfilaments provide mechanical resistance by 
pulling on the intact collagen. In response to this created 
tension, intracellular scaffolding composed of intermediate 
filaments and microtubules pushes outward to causing 
fibroblasts to stretch. This stretch is an essential cue for 
normal collagen and MMP production by fibroblasts (Figure 
2.4) [30]. 

This mechanical tension model is different in photoaged 
human skin. Fibroblast-integrin attachments are lost, which 
prevents collagen fragments from binding to fibroblasts. 
Collagen-fibroblast binding is crucial for maintenance of 
normal mechanical stability. When mechanical tension is 
reduced, as in photoaged skin, fibroblasts collapse, which 
causes decreased procollagen production and increased col- 
lagenase (COLase) production [30]. Collagen is continually 
lost as this cycle repeats itself. 


16 




































2. Photoaging 


Figure 2.3 Model depicting the effects of UV 
irradiation on epidermal keratinocytes (KC) and 
dermal fibroblasts (FB). AP-1, activator protein 1; 
MMP, matrix metalloproteinase. (Reproduced by 
permission of: Fisher GJ, et al. Mechanisms of 
photoaging and chronological skin aging. Arch 
Dermatol 2002; 138: figure 1 p. 1463. Copyright 
2002, American Medical Association. All Rights 
reserved.) 


Growth factor 
Cytokine receptors 



Cytokine receptors 

1 



MMPs 

1 

Dermal matrix breakdown 

i 

Imperfect repair —y Photoaging 


Figure 2.4 Fibroblasts have evolved to 
regulate their output of collagen based on 
internal mechanical tension. Model depicting 
the effects of mechanical tension on 
procollagen production in (a) sun-protected 
human skin versus (b) photodamaged human 
skin. (Reproduced by permission of: Fisher GJ, 
Varani J, Voorhees, JJ. Looking older. Arch 
Dermatol 2008; 144(5), figure 2, p. 669. 
Copyright 2008, American Medical 
Association. All rights reserved.) 


Intact 



Cross-links / 

K 



Collagen 

fragments 


X 


(b) Collapsed fibroblast 


Photoprotected or young skin 


Photoaged or aged skin 


17 


























BASIC CONCEPTS Skin Physiology 


Ethnic skin: photoaging 

All races are susceptible to photoaging. However, people 
with Fitzpatrick skin phototypes IV-VI are less susceptible 
to the deleterious effects of UV irradiation than people with 
a lower Fitzpatrick skin type classification. This phenome¬ 
non is most likely a result of the protective role of melanin 
[31]. Studies reporting ethnic skin photoaging are few and 
far between. However, for the purposes of this discussion, 
characteristics of photoaging in different ethnic skin catego¬ 
ries are briefly highlighted. 

In one of the first studies comparing UV absorption 
amongst different skin types, Kaidbey et al. [32] compared 
the photoprotective properties of African-American skin 
with Caucasian skin exposed to UVB irradiation. It was 
known that only 10% of the total UVB rays penetrated the 
dermis. However, the mean UVB transmission into the 
dermis by African-American dermis (3.7%) was found to 
be significantly less than for Caucasian dermis (29.4%). 
Similar experiments were performed with UVA irradiation. 
Although only 30% of the total UVA exposure penetrates 
into the papillary dermis, UVA transmission into African- 
American dermis was 17.5% compared to 55% for white 
epidermis [32]. The physiologic reason behind this differ¬ 
ence in black and white skin lies at the site of UV filtration. 
The malpighian layer (basal cell layer) of African-American 
skin is the main site of UV filtration, while the stratum 
corneum absorbs most UV rays in white skin. The mal¬ 
pighian layer of African-American skin removes twice as 
much UVB radiation as the overlying statum corneum, thus 
mitigating the deleterious effects of UV rays in the underly¬ 
ing dermis [33]. 

In African-Americans, photoaging may not be clinically 
apparent until the fifth or sixth decade of life and is more 
common in individuals with a lighter complexion [34]. The 
features of photoaging in this ethnic skin group manifest as 
signs of laxity in the malar fat pads sagging toward the 
nasolabial folds [35]. In patients of Hispanic and European 
descent, photoaging occurs in the same frequency as 
Caucasians and clinical signs are primarily wrinkling rather 
than pigmentary alterations. The skin of East and South-East 
Asian patients, on the contrary, mainly exhibits pigmentary 
alterations (seborrheic keratoses, hyperpigmentation, actinic 
lentigines, sun-induced melasma) and minimal wrinkling 
as a result of photoaging [36,37]. Finally, very few studies 
have reported on the signs of photoaging in South Asian 
(Pakistanis, Indians) skin. UV-induced hyperpigmentation, 
dermatosis papulosa nigra, and seborrheic keratosis are 
noted [38]. 

Despite all of these differences, it is important to note that 
the number of melanocytes per unit area of skin does not 
vary across ethnicities. Instead, it is the relative amount of 
melanin packaged into melanocytes that accounts for the 


physiologic differences between Caucasian skin and ethnic 
skin [39]. 


Prevention 

Although the effects of the sun's rays appear daunting, there 
are some ways to avoid the deleterious effects of photoaging. 
Avoiding photoaging can often prove to be more cost- 
effective than trying to reverse the signs of photoaging after 
they have manifested. 

Primary prevention 

Sun protection 

UV rays are especially prevalent during the hours of 1 0am- 
4pm and sun protection should be encouraged during this 
time. Sun protection can be offered to patients in the form 
of sunscreens, sun-protective clothing, and/or sun avoid¬ 
ance. Sun-protective clothing includes any hats, sunglasses, 
or clothing that would help block the sun's rays. 
Photoprotective clothing is given a UV protection factor 
(UPF) rating, which is a measurement of the amount of 
irradiation that can be transmitted through a specific type 
of fabric. A UPF of 40-50 is recommended by most derma¬ 
tologists, as it transmits less than 2.6% of UV irradiation [5]. 

Traditionally, sunscreens contain one or more chemical 
filters - those that physically block, reflect, or scatter specific 
photons of UV irradiation and those that absorb specific UV 
photons. UVA sunblocks contain the inorganic particulates 
titanium dioxide or zinc oxide, while UVA-absorbing sun- 
creens contain terephthalylidene dicamphor sulfonic acid or 
avobenzene. UVB-absorbing sunscreens can contain sali¬ 
cylates, cinnamates, /?-aminobenzoic acid, or a combination 
of these [40]. The US Food and Drug Administration (FDA) 
recommended dose of sunscreen application is 2 mg/cm 2 
[41]. 

The sun protection factor (SPF) is an international labora¬ 
tory measure used to assess the efficacy of sunscreens. The 
SPF can range from 1 to over 80 and indicates the time that 
a person can be exposed to UVB rays before getting sunburn 
with sunscreen application relative to the time a person can 
be exposed without sunscreen. SPF levels are determined by 
the minimal amount of UV irradiation that can cause UVB- 
stimulated erythema and/or pain. The effectiveness of a 
particular sunscreen depends on several factors, including 
the initial amount applied, amount reapplied, skin type of 
the user, amount of sunscreen the skin has absorbed, and 
the activities of the user (e.g. swimming, sweating). 

The sun protection factor is an inadequate determination 
of skin damage because it does not account for UVA rays. 
Although UVA rays have an important role in photoaging, 
their effects are not physically evident as erythema or pain, 
as are UVB rays. Therefore, it has been suggested that SPF 
may be an imperfect guide to the ability of a particular sun- 


18 




2. Photoaging 


UV 

i 


Figure 2.5 Model depicting the acute and chronic effects of 
UV irradiation on skin angiogenesis and extracellular matrix 
(ECM) degradation in human skin. MMP, matrix 
metalloproteinase; TSP, thrombospondin-1 (ECM protein; 
inhibitor of angiogenesis in epithelial tissues); VEGF, vascular 

endothelial growth factor. (Reproduced by permission of: Chronic effects 

Blackwell Publishing. This figure was published in: Chung JH, 

Eun HC. (2007) Angiogenesis in skin aging and photoaging. 

J Dermatol 34, figure 1, p. 596.) 


Acute effects 


i _ ± 


f Skin angiogenesis 


\ECM degradation 

t VEGF 


\ Collagen 

|tsp 


f MMPs 




Inflammation 

Worse environment 
for normal vasculature 


Photoaged human skin 
\ ECM (collagen fibers, 
elastic fibers) 

I Dermal vasculature 


screen to shield against photoaging [5]. As a result, combina¬ 
tion UVA-UVB sunscreens have been developed and are 
recommended to protect the human skin from both types of 
irradiation. 

Secondary prevention 

Retinoids 

A large number of studies have reported that topical applica¬ 
tion of 0.025-0.1% all -trans retinoic acid (tRA) improves 
photoaging in human skin [42,43]. Results vary based on 
treatment duration and applied tRA dose. Although there 
have been a variety of clinical trials on the topic, the mole¬ 
cular mechanisms by which tRA acts are still waiting to be 
discovered. Retinoic acids have been used in an ex post facto 
manner to reverse the signs of photodamage and in a pre¬ 
ventative fashion to avoid photoaging. 

More specifically, tRA has been shown to induce type I 
and III procollagen gene expression in photoaged skin [44]. 
It has been observed that topical tRA induces TGF-(3 in 
human skin [45], which stimulates the production of type I 
and III procollagen. 

In addition, tRA has been used in a preventive fashion to 
avert UV-induced angiogenesis. Kim etal. [20] demonstrated 
that topical application of retinoic acid before UV exposure 
inhibited UV-induced angiogenesis and increases in blood 
vessel density. In general, extracellular signal-related kinases 
(ERKs, or classic MAP kinases) positively regulate epider- 
mally derived VEGF. VEGF stimulates angiogenesis upon UV 
induction. Retinoic acid inhibits ERKs, which can potentially 
lead to downregulation of VEGF expression, UV-induced 
angiogenesis, and angiogenesis-associated photoaging 
(Figures 2.5 and 2.6) [16]. 

Finally, tRA has been reported to prevent UV-stimulated 
MMP expression. The transcription factor, c-Jun, is a key 


Aged and photoaged human skin 
i ECM (collagen fibers, elastic fibers) 
\ Dermal vasculature 

j j Retinoic acid 


* i 


\ECM degradation 


\Skin angiogenesis 

t Collagen 


t VEGF 

|MMPs 


t Vascularization 


V# 


Better environment 
for normal vasculature 

i 

Improve skin aging 


Figure 2.6 Model depicting the effect of topical retinoids on photoaged 
human skin. ECM, extracellular matrix; MMP, matrix metalloproteinase; 
VEGF, vascular endothelial growth factor. (Reproduced by permission of: 
Blackwell Publishing. This figure was published in: Chung J, Eun HC. 
(2007) Angiogenesis in skin aging and photoaging. J Dermatol 34, figure 
5, p. 599.) 


component in forming the AP-1 complex. Recall that the 
AP-1 complex both inhibits types I and III procollagen 
and stimulates transcription of MMPs. Retinoic acid blocks 
the accumulation of c-Jun protein, consequently inhibiting 
the formation of the AP-1 complex and dermal matrix- 
associated degradation [46]. 

Antioxidants 

It is important to highlight briefly the role of antioxi¬ 
dants in the reduction of photoaging. In vitro studies have 


19 
















BASIC CONCEPTS Skin Physiology 


discovered a large number of antioxidants that either fore¬ 
stall or reverse the clinical signs of photodamage caused by 
ROS. In vivo studies investigating these same antioxidants 
are ongoing. One such antioxidant, vitamin C, has been 
shown to mitigate photodamaged keratinocyte formation 
and erythema post-UV-irradiation [47]. 


Inherent defense mechanisms 

Although science has developed exogenous mechanisms to 
prevent and reverse the clinical signs of photoaging, the 
human skin possesses endogenous machinery built to 
protect the skin from UV-induced damage. These inherent 
defense mechanisms include, but are not limited to, increased 
epidermal thickness, melanin distribution, DNA repair 
mechanisms and apoptosis of sunburned keratinocytes, 
MMP tissue inhibitors, and antioxidants [5,32,48-50]. 


Failure of prevention: immunosuppression 

Although photoaging is the most prevalent form of skin 
damage, local and systemic immunosuppression, leading to 
skin carcinoma, can result from overexposure to the sun's 
rays. This immunosuppression is mediated by a combination 
of DNA damage, epidermal Langerhans' cell depletion, and 
altered cytokine expression [51,52]. 


Conclusions 

The pathophysiology of photoaging derives from the ability 
of UV irradiation to exploit established molecular mecha¬ 
nisms which have evolved to maintain the internal milieu 
of human skin connective tissue. Disruption of the normal 
skin architecture does not occur through one pathway, but 
rather is the culmination of several interdependent, but 
distinct, processes that have gone awry. The integrity of the 
normal dermal matrix is maintained through signaling 
transduction pathways, transcription factors, cell surface 
receptors, and enzymatic reactions that are intertangled and 
communicate with one another. When UV irradiation is 
introduced into this homeostatic picture, deleterious effects 
can be implemented. Production of ROS, inhibition of pro- 
collagen production, collagen degradation, and fibroblast 
collapse are only a few known processes amongst the medley 
of mechanisms still waiting to be discovered that contribute 
to photoaging. Although human skin is equipped with 
inherent mechanisms to protect against photoaging and 
methods of prevention and therapeutics are widely availa¬ 
ble, these alternatives are not absolute and do not necessar¬ 
ily guarantee a perfect escape from the sun's UV irradiation. 
With each passing day, scientists continue to discover 


novel cutaneous molecular mechanisms affected by UV 
irradiation and, consequently, search for new solutions to 
photodamage. 

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49 Oh JH, Chung AS, Steinbrenner H, Sies H, Brenneisen P. (2004) 
Thioredoxin secreted upon ultraviolet A irradiation modulates 
activities of matrix metalloproteinase-2 and tissue inhibitor of 
metalloproteinase-2 in human dermal fibroblasts. Arch Biochem 
Biophys 423, 218-26. 

50 Soter N. (1995) Sunburn and suntan: immediate manifestations 
of photodamage. In: Gilchrest B, ed. Photodamage. Cambridge, 
MA: Blackwell Science, pp. 12-25. 

51 Vink AA, Moodycliffe AM, Shreedhar V, Ullrich SE, Roza L, 
Yarosh DB, et al. (1997) The inhibition of antigen-presenting 
activity of dendritic cells resulting from UV irradiation of murine 
skin is restored by in vitro photorepair of cyclobutane pyrimi¬ 
dine dimers. Proc Natl Acad Sci USA 94, 5255-60. 

52 Toews GB, Bergstresser PR, Streilein JW. (1980) Epidermal 
Langerhans cell density determines whether contact hypersen¬ 
sitivity or unresponsiveness follows skin painting with DNFB. 
J Immunol 124, 445-53. 


21 


Chapter 3: Self-perceived sensitive skin 

Olivier de Lacharriere 

L'Oreal Recherche, Clichy, France 


BASIC CONCEPTS 

• Sensitive skin is a term used by individuals who perceive their skin as being more intolerant or reactive than the general 
population. 

• Sensitive skin is clinically characterized by subjective, sensorial signs: facial discomfort with stinging, burning, and itching. 

• The clinical signs of sensitive skin appear in specific conditions, provoked by reactivity factors: environmental factors: wind, sun, 
cold weather, fast changes in temperature; topical factors: hard water, cosmetics; internal factors: life stress, menstruation, or 
spicy or hot foods. 


Introduction 

Sensitive skin is a clinical syndrome, first described in the 
1960s by Thiers [1]. A protocol for clinical evaluation of 
sensitive skin using lactic acid sting testing was first intro¬ 
duced in the 1970s by Frosch and Kligman [2]. Subsequent 
to that, interest in the field of sensitive skin exploded based 
on "subjective discomfort, namely, delayed stinging from 
topical agents applied to the skin." In spite of the contrary 
opinion expressed by Maibach et al. [3] at the end of the 
1980s, that "the plausibility of the concept of the sensitive 
skin evokes discussion and often amusement because of the 
variance of the number of opinions compared with the 
amount of data, at least until recently," significant progress 
has been made on sensitive skin research in recent years. 
Based on current opinion, sensitive skin is now well accepted 
as a clinical syndrome. 

Based on consumer complaints, it is clear that sensitive 
skin is a term used by individuals who perceive their skin 
as being more intolerant or reactive than the general popu¬ 
lation. Consequently, sensitive skin could be defined as a 
hyperreactive skin, characterized by exaggerated sensorial 
reaction to environmental or topical factors, including hard 
water and cosmetics. Consequently, instead of "sensitive 
skin," it is better to call this syndrome "self-perceived sensi¬ 
tive skin" (SPSS). 

In the last decade, some new understanding on the mech¬ 
anisms of sensitive skin, involving sensitive epidermal nerves 
has been emphasized [4]. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Clinical features 

Clinical signs and provocative factor 

Sensitive skin is clinically characterized by subjective, senso¬ 
rial signs: facial discomfort with stinging, burning, and 
itching. SPSS is more frequent in young women, and 
decreases with age. 

The clinical signs of sensitive skin appear in specific condi¬ 
tions, provoked by reactivity factors: 

• Environmental factors: wind, sun, cold weather, fast 
changes in temperature; 

• Topical factors: hard water, cosmetics; 

• Internal factors: life stress, menstruation, or spicy or hot 
foods. 

Clinical subgroups 

Although the distribution of sensitive skin occurs through¬ 
out the population, multivariate analysis shows that several 
subgroups could be defined [4,3], according to the severity 
of sensitive skin and to the provocative factors: 

1 Severe sensitive skin; 

2 Sensitive skin to environment; 

3 Sensitive skin to topical factors. 

Severe sensitive skin 

Severe sensitive skin demonstrates very high facial skin 
reactivity to all kinds of factors: topical, environmental 
including atmospheric pollution and also internal factors 
such as stress and tiredness. Severe sensitive skin could 
present as "crisis phases" occurring for several days or weeks. 
During these phases, known as "status cosmeticus," the skin 
becomes intolerant to all applied products, even products 
that are usually very well tolerated by the consumer [6]. 


22 







3. Self-perceived sensitive skin 


Sensitive skin to topical factors 

Around 23% of women have sensitive skin to topical factors. 
In this subgroup of sensitive skin, the provocative factor is 
the application of a product on the skin. It is important to 
underline that the intolerance observed appears immedi¬ 
ately or in the minutes following application, sometimes 
from the first application. 

Sensitive skin to environmental factors 

Around 13-20% of women have sensitive skin to environ¬ 
mental factors such as heat, rapid changes in temperature, 
or wind. 

Diathesis factors 

In most cases of sensitive skin, the skin hyperreactivity is 
constitutional. Thiers [1], who was the first to describe this 
syndrome, has suggested that diathesis features could exist. 
We also found that a familiar history of sensitive skin exists. 
Sensitive skin is more frequently found in subjects with fair 
complexion, and/or redness on the cheekbones [7,8]. Severe 
dry skin could be as affected as severe oily skin by skin 
hyperreactivity. 

Acquired skin hyperreactivity could mimic the signs 
observed during sensitive skin syndrome. This acquired 
"sensitive skin," characterized by a temporary decrease of 
the threshold of sensorial reactivity of the skin, could be 
linked to topical irritants improperly applied such as retin¬ 
oids or hydroxy-acids. In these cases, it is possible that skin 
that is usually "non-reactive" becomes "reactive" for a 
period of time. The presence of active facial dermatitis such 
as seborrheic dermatitis or rosacea could also lower the 
threshold of skin reactivity. However, although an outbreak 
of facial atopic dermatitis increases skin reactivity, it is incor¬ 
rect to consider all sensitive skin as atopic skin. 

Sensitive skin and immuno-allergologic pattern 

An important point about sensitive skin comes from contro¬ 
versial opinions that exist regarding allergic status [5,7]. To 
explore this, skin patch test reactivity was studied in 152 
female adult volunteers [9]. Eighty-eight declared them¬ 
selves as having sensitive skin, and 64 as having non¬ 
sensitive skin. 

A series of 44 different topical ingredients known to be 
potential allergens were applied to the back under Finn 
Chambers (Table 3.1). The patches were removed after 47 
hours and the reactions read after 1 hour and 2 days. For 
each ingredient, the incidence of positive reactions was com¬ 
pared between the two populations, using the % 2 test. Positive 
reactions were recorded for 19 out of the 44 tested com¬ 
pounds. No significant difference in the incidence of positive 
reactions was found between sensitive and non-sensitive 
skin subjects for any of the patch-tested ingredients. 

Currently, sensitive skin must not be considered as a 
syndrome linked to an immuno-allergologic pattern. 


Table 3.1 List of tested allergens on self-perceived sensitive skin and 
non-self-perceived sensitive skin subjects. (From [4] and [9].) 


Diazolidinyl urea 

Hydroquinone 

Colophon 

Cocamidopropylbetaine 

Formaldehyde 

Ethylene diamine 

Balsam of Peru 

Ortho-aminophenol 

Benzoic acid 

Glyceryl monothioglycolate 

Pyrogallol 

Ammonium thioglycolate 

Parabens mix 

Dowicil 

Ammonium persulfate 

Isothiazolinones 

p-aminodiphenylamine 

Fragance mix 

Wool alcohols 



Diagnosis 

Provocative tests 

The diagnosis of SPSS must be based on clinical signs, which 
are neurosensorial (i.e. subjective). In fact, facial stinging, 
burning, and itching are clinical signs directly felt by the 
subject but not seen by the observer. It corresponds to the 
concept of "invisible dermatoses" [10], as is also the case for 
all sensorial signs encountered in dermatology (e.g. itching, 
pain). 

Pertinent clinical questionnaires are probably the best 
tools to diagnose this syndrome. Provocative tests could be 
of help. 

The lactic acid stinging test was first described by Frosch 
and Kligman [2,11]. A solution of 10% lactic acid is applied 
to a nasolabial fold and the provoked stinging feeling is 
quantified. Generally, the stinging is measured every minute 
for 5 minutes on a scale from 0 to 3. The lactic acid reaction 
is compared with the other nasolabial fold where a control 
solution (saline solution) is applied. The test discriminates 
between "stingers" and "non-stingers," but does not affect 
the discrimination between sensitive skin and non-sensitive 
skin subjects [12]. In our opinion, the lactic acid stinging test 
is of interest to assess efficacy of products, but not for diag¬ 
nostic purposes. 

Considering the clinical signs linked to SPSS (stinging, 
burning, itching), we have hypothesized that the main 
player is the sensitive epidermal nerve, C-fibers [13]. 
According to this physiologic hypothesis, we have proposed 
to test the skin reactivity by using capsaicin [14], an irritant 
compound extracted from red pepper which acts on vanil- 
loid receptors of the nociceptive C-fibres and provokes the 
release of neuropeptides as substance P and calcitonin gene- 
related peptide (CGRP) [15,16]. 


23 




BASIC CONCEPTS Skin Physiology 


Capsaicin cream (0.075%) was applied at the angle of the 
jaw over an area of 4cm 2 . The neurosensorial signs (stinging, 
burning, and itching [SBI]) were assessed at 3, 5, 10, 15 and 
20minutes according to a scale score (0, 1, 2, 3). The sum 
of the scores gives the global SBI score. 

The results we obtained on two groups of subjects clearly 
showed that the sensitive skin subjects' (n = 64) reactions 
were significantly higher than the non-sensitive subjects 
(n = 88) (Figure 3.1). The capsaicin test allows one to dis¬ 
criminate quite well between SPSS subjects and non-SPSS 
subjects. 

On the same population sample, we compared the 
scores obtained with the capsaicin test with those from 
the lactic acid stinging test. The results are presented in 
Table 3.2. With capsaicin, the scores showed a better 
correlation to the SPSS than those recorded with lactic 
acid. Furthermore, there is a real relationship between 
the severity of the sensitive skin and the response to the 
capsaicin test. The higher the severity of SPSS, the higher 
the capsaicin score. 


Global discomfort (stinging + burning + itching) 



Figure 3.1 Stinging, burning, and itching (SBI) score with capsaicin test 
on self-perceived sensitive skin and non-self-perceived sensitive skin 
subjects. Scores are significantly different at each experimental time 
(p < 0.01). (From [4] and [14].) 


Sensitive skin and populations 
Epidemiologic data 

The prevalence of SPSS is estimated at 51-56% in Europe, 
USA, and Japan [8,17-20]. 

Willis et al. [8] published an epidemiologic study in the 
UK on sensitive skin where 2058 people (up to 18 years of 
age) were investigated. Of those who reposonded, 51% of 
the women and 38% of the men declared themselves to 
have sensitive skin. 

In the San Francisco area, the reported prevalence of SPSS 
in four ethnic groups (African-American, Asian, Euro- 
American, and Hispanic Central American) is 52% [19]. No 
significant difference of prevalence in each group was found: 
52% of African-Americans had sensitive skin, 51% of 
Asians, 50% of Euro-Americans, and 54% of South 
Americans. 

Yang et al. [21] studied the sensitive skin in four cities of 
China: Beijing and Harbin (northern cities), Chengdu and 
Suzhou (southern cities). Two thousand Chinese women, 
aged 18-75 years, were included. The global prevalence of 
sensitive skin was 36%. The prevalence decreases with age 
(47% at 21-25 years; 20.8% at 51-55 years). 

Clinical features 

Although the comparison of groups living in San Francisco 
(African-Americans, Asians, Euro-Americans, and Hispanics) 
gave the same prevalence of sensitive skin (52%), some 
differences (10) were observed for factors of skin reactivity 
and, to a lesser extent, its clinical symptoms. Euro- 
Americans were characterized by higher skin reactivity to 
the wind and tended to be less reactive to cosmetics. 
African-Americans presented less skin reactivity to most 
environmental factors and a lower frequency of recurring 
facial redness. Asians appeared to have greater skin reactiv¬ 
ity to sudden changes in temperature, to the wind, and 
also to spicy foods. They tended to experience itching more 
frequently. In addition, the frequency of skin reactivity to 
alcoholic beverages was significantly lower in the African- 


Table 3.2 (a) Stinging and itching scores with capsaicin test according to the different self- 
assessed level of self-perceived sensitive skin. (From [4].) 


Non-sensitive 
(n = 64) 

Sensitive (n 

= 88) 


Significance 


Weak 

(n = 42) 

Medium 

(n = 39) 

Strong 
(n = 7) 


Stinging 

2.6 ± 0.6 

3 ± 0.6 

4.3 ± 0.6 

5 ± 0.6 

p < 0.02 

Itching 

0.6 ± 0.4 

1.6 ±0.4 

2 ± 0.4 

2.9 ± 0.4 

p < 0.02 



24 
















3. Self-perceived sensitive skin 


Table 3.2 (b) Stinging scores during lactic acid stinging test 
according to the different self-assessed level of self-perceived sensitive 
skin. (From [4].) 


Non-sensitive 

(n = 64) 

Sensitive (n = 88) 


Significance 

Weak 
(n = 42) 

Medium 
(n = 39) 

Strong 
(n = 7) 


2 ± 0.3 

2 ± 0.2 

3.3 ±0.3 

3 ± 0.3 




p< 0.001 

p< 0.001 

p< 0.01 


American and Hispanic sensitive groups and higher in the 
Asian group. 

In China, Yang et al. [21] have reported that sensitive skin 
was strongly reactive to environmental factors, but not to 
cosmetic use. A significantly higher prevalence (33.8%) of 
sensitive skin was found in Chengdu (Sichuan), where the 
food is very spicy. By studying the link between chili con¬ 
sumption and sensitive skin prevalence, it has been con¬ 
firmed that sensitive skin was strongly linked to spicy food 
intake. 


Physiologic mechanisms involved in self- 
perceived sensitive skin 

Barrier function and sensitive skin 

It is currently believed that sensitive skin is linked to the 
skin barrier alteration which could explain the increase in 
skin reactivity to physical or chemical factors. 

In fact, transepidermal water loss (TEWL) has been 
reported to be increased in subjects with sensitive skin [18]. 
In addition, an increase in TEWL has also been reported in 
the "lactic acid stingers" subjects [12]. The alteration of the 
skin barrier function is certainly involved in the physiology 
of some patterns of sensitive skin, but it is not 
unequivocal. 

Epidermal sensitive nerves and sensitive skin 

In the last decade, additional evidence has been discovered 
implicating the key role for sensitive nerves in the physio¬ 
logic mechanisms involved in sensitive skin. 

The neurosensorial signs of the pattern of capsaicin reac¬ 
tivity of sensitive skin suggest a neurogenic origin [14]. 
Recent data that emphasize the role of C-fibres in the itching 
process must also be considered [13]. 

It is observed that there is a decrease with age in the epi¬ 
dermal sensitive nerve density on the face [22]. It should 
also be noticed that there is a similar decrease in the facial 
skin reactivity to capsaicin and in the prevalence of sensitive 


skin, suggesting a direct involvement of epidermal sensitive 
nerves in skin reactivity. 

Specific brain activation on sensitive skin subjects 

To investigate the possible involvement of the central 
nervous system (CNS) in SPSS patterns, we measured cer¬ 
ebral responses to cutaneous provocative tests in sensitive 
and in non-sensitive skin subjects using functional magnetic 
resonance imaging (fMRI) [23]. According to their responses 
to validated clinical questions about their skin reactivity, 
subjects were divided into two balanced groups: severe SPSS 
and non-SPSS subjects. Event-related fMRI was used to 
measure cerebral activation induced by split-face application 
of lactic acid and of its vehicle (control). In sensitive skin 
subjects, prefrontal and cingulate activity was significantly 
higher demonstrating a CNS involvement in sensitive skin 
physiologic pathways. 


Conclusions 

Sensitive skin is a syndrome observed all over the world. 
The key clinical features of sensitive skin are neurosensorial 
signs, mainly provoked by climatic factors, or by topical 
applications usually well-tolerated on skin. 

The hypothesis of the neurogenic origin of sensitive skin 
is becoming more and more predominant. 

1 Sensitive skin subjects demonstrate a significantly higher 
skin hyperreactivity to capsaicin which specifically stimu¬ 
lates the C-fibers. 

2 With age, as sensitive skin is decreasing, facial sensitive 
epidermal nerve density is also decreasing. 

3 Spicy food (rich in capsaicin) increases the prevalence of 
sensitive skin. 

4 The results obtained with fMRI show that sensitive skin 
subjects demonstrate a specific pattern on cerebral activa¬ 
tion, with a higher brain activity for sensitive skin subjects 
in prefrontal and cingulated areas. 

References 

1 Thiers H. (1986) Peaii sensible. In: H. Thiers. Les Cosmetiques, 2nd 
edn. Paris: Masson, pp. 266-8. 

2 Frosch PJ, Kligman AM. (1977) A method of appraising the 
stinging capacity of topically applied substances. J Soc Cosmet 
Chem 28, 197-209. 

3 Maibach HI, Lammintausta K, Berardesca E, Freeman S. (1989) 
Tendancy to irritation: sensitive skin. J Am Acad Dermatol 21, 
833-5. 

4 De Lacharriere O. (2006) Sensitive skin: a neurological perspec¬ 
tive. 24th IFSCC, Osaka, October 2006. 

5 Francomano M, Bertoni L, Seidenari S. (2000) Sensitive skin as 
a subclinical expression of contact allergy to nickel sulfate. 
Contact Dermatitis 42, 169-70. 

6 Fisher AA. (1990) Part I: "Status cosmeticus": a cosmetic intoler¬ 
ance syndrome. Cutis 46, 109-11016. 


25 








BASIC CONCEPTS Skin Physiology 


7 De Lacharriere O, Jourdain R, Bastien P, Garrigue JL. (2001) 
Sensitive skin is not a subclinical expression of contact allergy. 
Contact Dermatitis 44, 131-2. 

8 Willis CM, Shaw S, De Lacharriere O, Baverel M, Reiche L, 
Jourdain R, et al. (2001) Sensitive skin: an epidemiological 
study. Br J Dermatol 145, 258-63. 

9 Jourdain R, De Lacharriere O, Shaw S, Reiche L, Willis C, 
Bastien P, etal. (2002) Does allergy to cosmetics explain sensitive 
skin? Ann Dermatol Venereol 129, 1S11-77. 

10 Kligman AM. (1991) The invisible dermatoses. Arch Dermatol 
127, 1375-82. 

11 Frosch P, Kligman AM. (1996) An improved procedure for con¬ 
ducting lactic acid stinging test on facial skin. J Soc Cosmet Chem 
47, 1-11. 

12 Seidenari S, Francomano M, Mantovani L. (1998) Baseline 
biophysical parameters in subjects with sensitive skin. Contact 
Dermatitis 38, 311-5. 

13 Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjork 
HE. (1997) Specific C-receptors for itch in human skin. JNeurosci 
17, 8003-8. 

14 de Lacharriere O, Reiche L, Montastier C, et al. (1997) Skin 
reaction to capsaicin: a new way for the understanding of 
sensitive skin. Australas J Dermatol 38(Suppl 2), 288. 

15 Magnusson BM, Koskinen LO. (1996) Effects of topical applica¬ 
tion of capsaicin to human skin: a comparison of effects evalu¬ 
ated by visual assessment, sensation registration, skin blood flow 


and cutaneous impedance measurements. Acta Derm Venereol 76, 
29-32. 

16 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine 
JD, Julius D. (1997) The capsaicin receptor: a heat-activated ion 
channel in the pain pathway. Nature 389, 816-24. 

17 Johnson AW, Page DJ. (1995) Making sense of sensitive skin. 
Proceedings of the 18th IFSCC Congress, Yokohama, Japan 
1995. 

18 Morizot F, Le Fur I, Tschachler E. (1998) Sensitive skin: defini¬ 
tion, prevalence and possible causes. Cosm Toil 113, 59-66. 

19 Jourdain R, De Lacharriere O, Bastien P, Maibach HI. (2002) 
Ethnic variations in self-perceived sensitive skin: epidemiologi¬ 
cal survey. Contact Dermatitis 46, 162-9. 

20 Morizot F, Le Fur I, Numagami K, Guinot C, Lopez S, Tagami 
H, etal., eds. Self-reported sensitive skin: a study on 120 healthy 
Japanese women. 22nd IFSCC, Edinburgh, September 2002. 

21 Yang FZ, De Lacharriere O, Lian S, Yang ZL, Li L, Zhou W, et al. 
(2002) Sensitive skin: specific features in Chinese skin: a clinical 
study on 2,000 Chinese women. Ann Dermatol Venereol 129, 
1S11-77. 

22 Besne I, Descombes C, Breton L. (2002) Effect of age and 
anatomical site on density innervation in human epidermis. 
Arch Dermatol 138, 1445-50. 

23 Querleux B, Dauchot K, Jourdain R, Bastien P, Bittoun J, Anton 
JL, et al. (2008) Neural basis of sensitive skin: an fRMI study. 
Skin Res Technol 1, 1-8. 


26 


Chapter 4: Pigmentation and skin of color 

Chesahna Kindred and Rebat M. Haider 

Howard University College of Medicine, Washington, DC, USA 


BASIC CONCEPTS 

• Differences in the structure, function, and physiology of the hair and skin in individuals of skin of color are important in 
understanding the structural and physiologic variations that exist and influence disease presentations. 

• Melanin, the major determinant of skin color, absorbs UV light and blocks free radical generation, protecting the skin from sun 
damage and aging. 

• UV irradiation of keratinocytes induces pigmentation by the upregulation of melanogenic enzymes, DNA damage that induces 
melanogenesis, increased melanosome transfer to keratinocytes, and increased melanocyte dendricity. 

• Racial differences in hair include the hair type, shape, and bulb. 


Introduction 

The demographics of the USA reflect a dynamic mixture of 
people of various ethnic and racial groups. Currently, one 
in three residents in the USA is a person of skin of color [1]. 
Persons of skin of color include Africans, African-Americans, 
Afro-Caribbeans, Asians, Latinos (Hispanics), Native 
Americans, Middle Easterners, and Mediterraneans. The 
term "black" as in black skin refers to individuals with 
African ancestry, including Africans, African-Americans, 
and Afro-Caribbeans. Subgroups exist within each ethnora- 
cial group. The differences in the structure, function, and 
physiology of the hair and skin in individuals of skin of color 
are important in understanding the structural and physio¬ 
logic variations that exist and influence disease presenta¬ 
tions. Pigmentation is especially important in patients of skin 
of color because pigmentary disorder is the most common 
reason for a visit to a dermatologist in this group [2]. 


Melanocytes 

Melanin, the major determinant of skin color, absorbs UV 
light and blocks free radical generation, protecting the skin 
from sun damage and aging. Melanocytes, the cells that 
produce melanin, synthesize melanin in special organelles, 
melanosomes. Melanin-filled melanosomes are transferred 
from one melanocyte to 30-35 adjacent keratinocytes in the 
basal layer [3]. The number of melanocytes also decreases 
with age. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


There is more than one type of melanin: eumelanin, a 
dark brown-black pigment; and pheomelanin, a yellow- 
reddish pigment. Eumelanin is deposited in ellipsoidal 
melanosomes which contain a fibrillar internal structure. 
Synthesis of eumelanin increases after UV exposure 
(tanning). Pheomelanin has a higher sulfur content than 
eumelanin because of the sulfur-containing amino acid 
cysteine. Pheomelanin is synthesized in spherical melano¬ 
somes and is associated with microvesicles [4]. Although not 
obvious to the naked eye, most melanin pigments of the 
hair, skin and, eyes are combinations of eumelanin and 
pheomelanin [5]. It is generally believed that genetics deter¬ 
mine the constitutive levels of pheomelanin and eumelanin. 
Eumelanin is more important in determining the degree of 
pigmentation than pheomelanin. Eumelanin, and not phe¬ 
omelanin, increases with visual pigmentation [5]. Lighter 
melanocytes have higher pheomelanin content than dark 
melanocytes. In one study [5], white persons had the least 
amount of eumelanin, Asian Indians had more, and African- 
Americans had the highest. Of note, adult melanocytes 
contain significantly more pheomelanin than cultured neo¬ 
natal melanocytes. 

Melanosomes also differ among different races. In black 
persons they are mostly in the basal layer, but those of white 
persons are mostly in the stratum corneum. This is evident 
in the site of UV filtration: the basal and spinous layers in 
blacks and the stratum corneum in white persons. Of note, 
the epidermis of black skin rarely shows atrophied areas [6]. 
In black skin, melanocytes contain more than 200 
melanosomes. The melanosomes are 0.5-0.8 mm in diame¬ 
ter, do not have a limiting membrane, are stuck closely 
together, and are individually distributed throughout the 
epidermis. In white skin, the melanocytes contain less than 
20 melanosomes. The melanosomes are 0.3-0.5 mm in 


27 








BASIC CONCEPTS Skin Physiology 


diameter, associated with a limiting membrane, and distrib¬ 
uted in clusters with spaces between them. The melano- 
somes of lighter skin degrade faster than that of dark skin. 
As a result, there is less melanin content in the upper layers 
of the stratum corneum. Thus, the melanocytes in black skin 
are larger, more active in making melanin, and the melano- 
somes are packaged, distributed, and broken down differ¬ 
ently from in white skin. 

There is also a difference in melanosomes between indi¬ 
viduals within the same race but with varying degrees of 
pigmentation. Despite greater melanin content in darker 
skins, there is no evidence of major differences in the 
number of melanocytes [7]. Also, dark Caucasian skin 
resembles the melanosome distribution observed in black 
skin [8]. Black persons with dark skin have large, non- 
aggregated melanosomes and those with lighter skin 
have a combination of large non-aggregated and smaller 
aggregated melanosomes [9]. White persons with darker 
skin have non-aggregated melanosomes when exposed 
to sunlight and white persons with lighter skin have 
aggregated melanosomes when not exposed to sunlight 
[7,8,10]. 

The steps of melanogenesis are as follows. The enzyme 
tyrosinase hydroxylates tyrosine to dihydroxyphenylalanin 
(DOPA) and oxidizes DOPA to dopaquinone. Dopaquinone 
then undergoes one of two pathways. If dopaquinone binds 
to cysteine, the oxidation of cysteinyldopa produces phe- 
omelanin. In the absence of cysteine, dopaquinone sponta¬ 
neously converts to dopachrome. Dopachrome is then 
decarboxylated or tautomerized to eventually yield eumela- 
nin. Melanosomal P-protein is involved in the acidification 
of the melanosome in melanogenesis [11]. Finally, the 
tyrosinase activity (not simply the amount of the tyro¬ 
sinase protein) and cysteine concentration determine the 
eumelanin-pheomelanin content [5]. 

Tyrosinase and tyrosinase-related proteins 1 and 2 (TRP-1 
and TRP-2) are upregulated when a-melanocyte-stimulating 
hormone (a-MSH) or adrenocorticotropin binds to melano- 
cortin-1 receptor (MC1R), a transmembrane receptor 
located on melanocytes [11-14]. The MC1R loss-of- 
function mutation increases sensitivity to UV-induced 
DNA damage. Gene expression of tyrosinase is similar 
between black and white persons, but other related genes 
are expressed differently. The MSH cell surface receptor 
gene for melanosomal P-protein is expressed differently 
between races. This gene may regulate tyrosinase, TRP-1, 
and TRP-2 [5]. 

In addition to the MC1R, protease-activated receptor 2 
(PAR-2) is another important receptor that regulates epider¬ 
mal cells and affect pigmentation [15]. PAR-2 is expressed 
on many cells and several different organs. Accordingly, the 
receptor is involved in several physiologic processes, includ¬ 
ing growth and development, mitogenesis, injury responses, 
and cutaneous pigmentation. In the skin, PAR-2 is expressed 


in the keratinocytes of the basal, spinous, and granular 
layers of the epidermis, endothelial cells, hair follicles, mye- 
oepithelial cells of sweat glands, and dermal dendritic-like 
cells [16,17]. PAR-2 is a seven transmembrane domain 
G-protein-coupled receptor which undergoes activation via 
proteolytic cleavage of the NH2 terminus which acts as a 
tethered ligand which then activates the receptor 
(autoactivation). 

PAR-2 activating protease (PAR-2-AP), endothelial cell- 
released trypsin, mast cell-released trypsin and chymase, 
and SLIGKV all irreversibly activate PAR-2 while serine pro¬ 
tease inhibitors interferes with the activation of the receptor 
[18-20]. SLIGKV and trypsin activate PAR-2 to use a Rho- 
dependent signaling pathway to induce melanosomal 
phagocytosis by keratinocytes. The result is an increase in 
pigmentation to the same degree as UV radiation [17-21]. 
Serine proteases are regulatory proteins involved in tumor 
growth, inflammation, tissue repair, and apoptosis in various 
tissues [17]. In the skin, serine protease inhibitors prevent 
the keratinocytes from phagocytosing melanosomes from 
the presenting dendritic tip of the melanocyte. This leads to 
a dose-dependent depigmentation without irritation or 
adverse events. 

PAR-2 also has a proinflammatory affect in the skin [17]. 
The activation of PAR-2 expressed on endothelial cells by 
tryptase, trypsin, or PAR-2-AP leads to an increase in proin¬ 
flammatory cytokines interleukin 6 (IL-6) and IL-8 and also 
stimulates NF-kB, an intracellular proinflammatory regula¬ 
tor [18]. Mast cells interact with endothelial cells to regulate 
inflammatory responses, angiogenesis, and wound healing, 
and PAR-2 has a regulatory role in this cell-cell interaction 
[17,18]. 

UV irradiation of keratinocytes induces pigmentation in 
several ways: upregulation of melanogenic enzymes, DNA 
damage that induces melanogenesis, increased melanosome 
transfer to keratinocytes and increased melanocyte dendric- 
ity. UV radiation (UVR) increases the secretion of proteases 
by keratinocytes in a dose-dependent manner. Specifically, 
UVR directly increases the expression of PAR-2 de novo , 
upregulates proteases that activate PAR-2, and activates 
dermal mast cell degranulation [21]. 

Data on whether PAR-2 is expressed differently in skin 
of color compared to white skin are needed. One study 
did find differences in skin phototypes I, II, and III [21]. 
UVR increases the expression of PAR-2 in the skin and 
activated PAR-2 stimulates pigmentation. This study found 
that the response of PAR-2 to UVR is an important deter¬ 
minant of one's ability to tan. In the non-irradiated skin, 
PAR-2 expression was confined to the basal layer and 
just above the basal layer. Irradiated skin showed de novo 
PAR-2 expression in the entire epidermis or upper two- 
thirds of the epidermis. Skin phototype I had a delayed 
upregulation of PAR-2 expression compared to phototypes 
II and III. 


28 


4. Pigmentation and skin of color 


Dyspigmentation 

After cutaneous trauma or inflammation, melanocytes can 
react with normal, increased, or decreased melanin produc¬ 
tion; all of which are normal biologic responses. Increased 
and decreased production results in postinflammatory 
hyperpigmentation or hypopigmentation. Postinflammatory 
hyperpigmentation (PIH) is an increase in melanin produc¬ 
tion and/or an abnormal distribution of melanin resulting 
from inflammatory cutaneous disorders or irritation from 
topical medications [22,23]. Examples include acne, allergic 
contact dermatitis, lichen planus, bullous pemphigoid, 
herpes zoster, and treatment with topical retinoids. Often, 
the PIH resulting from acne is more distressing to darker 
skinned individuals than the initial acute lesion. The color 
of the hyperpigmentation in PIH depends on the location of 
the melanin. Melanin in the epidermis appears brown, while 
melanin in the dermis appears blue-gray. Wood's lamp 
examination distinguishes the location of the melanin: the 
epidermal component is enhanced and the dermal compo¬ 
nent becomes unapparent [24]. Postinflammatory hypopig¬ 
mentation shares the same triggers as PIH but instead results 
from decreased melanin production with clinically apparent 
light areas [23]. The Wood's lamp examination does not 
accentuate hypopigmentation in postinflammatory hypop¬ 
igmentation; it is useful for depigmented disorders such as 
vitiligo and piebaldism. 

The pathogenesis of PIH and postinflammatory hypopig¬ 
mentation are unknown. It is likely that an inflammatory 
process in the skin stimulates keratinocytes, melanocytes, 
and inflammatory cells to release cytokines and inflamma¬ 
tory mediators that lead to the hyperpigmentation or hypo¬ 
pigmentation. The cytokines and inflammatory mediators 
include leukotriene (LT), prostaglandins (PG), and throm¬ 
boxane (TXB) [23]. Specifically for PIH, in vitro studies 
revealed that LT-C4, LT-D4, PG-E2, and TXB-2 stimulate 
human melanocyte enlargement and dendrocyte prolifera¬ 
tion. LT-C4 also increases tyrosinase activity and mitogenic 
activity of melanocytes. Transforming growth factor-a and 
LT-C4 stimulate movement of melanocytes. In postinflam¬ 
matory hypopigmentation, the pathogenesis likely involves 
inflammatory mediators inducing melanocyte cell-surface 
expression of intercellular adhesion molecule 1 (ICAM-1) 
which may lead to leukocyte-melanocyte attachments that 
inadvertently destroy melanocytes. These inflammatory 
mediators include interferon-gamma, tumor necrosis factor 
a (TNF-oc), TNF-(3, IL-6, and IL-7. 


Natural sun protective factor in skin of color 

It is clear that those who fall within Fitzpatrick skin photo¬ 
types IV-VI are less susceptible to photoaging; this is most 


likely due to of the photoprotective role of melanin [26,27]. 
The epidermis of black skin has a protective factor (PF) for 
UVB of 13.4 and that of white skin is 3.4 [28]. The mean 
UVB transmission by black epidermis is 3.7% compared 
to 29.4% for white epidermis. The PF for UVA in black 
epidermis is 5.7 and in white epidermis is 1.8 [28]. The 
mean UVA transmission by black epidermis is 17.5% and 
55.5% for white epidermis. Hence, 3-4 times more UVA 
reaches the upper dermis of white persons than that of black 
persons. 

The main site of UV filtration in white skin is the stratum 
corneum, whereas in black skin it is the basal layer [28]. 
The malphigian layer of black skin removes twice as much 
UVB radiation as the stratum corneum [29]. It is possible 
that even greater removal of UVA occurs in black skin basal 
layers [29]. While the above characteristics of natural sun 
protective factor were studied in black skin, they can prob¬ 
ably be extrapolated to most persons of skin photoypes 
IV-VI. 


Skin of color 

Epidermis 

The epidermal layer of skin is made up of five different 
layers: stratum basale, stratum spinosum, stratum granulo- 
sum, stratum lucidum, and stratum corneum. The stratum 
basale (also termed the basal layer) is the germinative layer 
of the epidermis. The time required for a cell to transition 
from the basal layer through the other epidermal layers to 
the stratum corneum is 24-40 days. The morphology and 
structure of the epidermis is very similar among different 
races, although a few differences do exist. 

Stratum corneum 

The stratum corneum, the most superficial layer, is the layer 
responsible for preventing water loss and providing mechan¬ 
ical protection. The cells of the stratum corneum, the cor- 
neocytes, are flat cells measuring 50 pm across and 1pm 
thick. The corneocytes are arranged in layers; the number 
of layers varies with anatomic site and race. There are no 
differences between races in corneocyte surface area, which 
has a mean size of 900 pm [2,30]. The stratum corneum of 
black skin is more compact than that of white skin. While 
the mean thickness of the stratum corneum is the same in 
black and white skin, black skin contains 20 cell layers 
while white skin contains 16. The answer to whether or 
not there are racial differences in spontaneous desquama¬ 
tion is inconclusive [29-31]. Parameters for skin barrier 
function (stratum corneum hydration, sebum secretion, 
erythema, and laser Doppler flowmetry) are similar, even 
after an objective epicutaneous test with sodium lauryl 
sulfate [32]. 


29 





BASIC CONCEPTS Skin Physiology 


Transepidermal water loss 

Transepidermal water loss (TEWL) is the amount of water 
vapor loss from the skin, excluding sweat. TEWL increases 
with the temperature of the skin. Concrete evidence regard¬ 
ing the difference in TEWL between different races has yet 
to be established. Aside from TEWL, hydration is also a 
characteristic of skin. One of the ways to measure hydration, 
or water content, is conductance. Conductance, the opposite 
of resistance, is increased in hydrated skin because hydrated 
skin is more sensitive to the electrical field [33]. Skin con¬ 
ductance is higher in black persons and Hispanics than white 
persons [33]. Lipid content in black skin is higher than that 
of white skin [34]. However, black skin is more prone to 
dryness, suggesting that a difference in lipid content has a 
role. This includes the ratio of ceramide: cholesterol: fatty 
acids, the type of ceramides, and the type of sphingosine 
backbone. One study suggests that the degree of pigmenta¬ 
tion influences lipid differences [33]. 

Pigmentation affects skin dryness. Skin dryness is greater 
on sun-exposed (dorsal arm) sites for lighter skin, such as 
Caucasian and Chinese skin, than sites that are primarily out 
of the sun (ventral arm) [36]. There is no difference in skin 
dryness between sites for darker skin, such as African- 
Americans and Mexicans. For adults less than 31 years of 
age, skin dryness does not change as a function of ethnicity 
(African-American, Caucasian, Chinese, and Mexican) for 
sun-exposed sites and sites that are not primarily sun- 
exposed. For those 51 years of age and older, skin dryness 
is higher for African-Americans and Caucasians than for 
Chinese and Mexicans. As a function of age, skin dryness in 
African-American skin increases 4% on the dorsal site and 
3% on the ventral site; in Caucasian skin, it increases 11% 
on the dorsal site and 10% on the ventral site. All of the 
above findings suggest that sun exposure can dry the skin 
and that melanin provides protection. 

Skin reactivity 

Mast cells 

Sueki et al. [37] studied the mast cells of four African- 
American men and four white men (mean age 29 years) by 
evaluating punch biopsies of the buttocks with electron 
microscopy, with the following results. The mast cells of 
black skin contained larger granules (the authors attributed 
this to the fusion of granules). Black skin also had 15% more 
parallel-linear striations and 30% less curved lamellae in 
mast cells. Tryptase reactivity was localized preferentially 
over the parallel-linear striations and partially over the dark 
amorphous subregions within granules of mast cells from 
black skin, whereas it was confined to the peripheral area 
of granules, including curved lamellae, in white skin. 
Cathepsin G reactivity was more intense over the electron- 
dense amorphous areas in both groups, while parallel-linear 
striations in black skin and curved lamellae in white skin 
were negative. 


Patch test antigens 
Contact dermatits 

Irritant contact dermatitis (ICD) is the most common form 
of dermatitis and loosely defined as non-specific damage to 
the skin after exposure to an irritant. The various clinical 
manifestations are influenced by the concentration of chem¬ 
icals, duration of exposure, temperature, humidity, and ana¬ 
tomic location, and other factors. Acute contact dermatitis 
presents with the classic findings of localized superficial ery¬ 
thema, edema, and chemosis. Cumulative contact dermatitis 
presents with similar findings, but with repeated exposure 
of a less potent irritant [38]. 

The susceptibility to ICD differs between black and white 
skin [39]. The structural differences in stratum corneum of 
black skin (e.g. compact stratum corneum, low ceramide 
levels) are credited with decreasing the susceptibility to irri¬ 
tants. Reflectance confocal microscopy (RCM) is an imaging 
tool that permits real-time qualitative and quantitative study 
of human skin; when used with a near-infrared laser beam, 
one can create "virtual sections" of live tissue with high 
resolution, almost comparable with routine histology. 
Measuring skin reactivity to chemical irritants with RCM 
and TEWL reveal that white skin had more severe clinical 
reactions than black skin. The pigmentation in darker skin 
can make the assessment of erythema difficult and interfere 
with identification of subclinical degrees of irritancy. Even 
without clinical evidence of irritation, RCM and histology 
reveal parakeratosis, spongiosis, perivascular inflammatory 
infiltrate, and microvesicle formation. Mean TEWL after 
exposure to irritants is greater for white skin than for black 
skin. This supports the concept that the stratum corneum of 
black skin enhances barrier function and resistance to 
irritants. 

There are no differences between white persons and 
African-Americans in objective and subjective parameters of 
skin such as dryness, inflammation, overall irritation, 
burning, stinging, and itching [40]. Acute contact dermatitis 
with exudation, vesiculation, or frank bullae formation is a 
more common reaction in white skin whereas dyspigmenta- 
tion and lichenification is more common in black skin [41]. 

The response to irritation in Caucasian and African- 
American skin differs in the degree of severity. Caucasian 
skin has a lower threshold for cutaneous irritation than 
African-American skin [42]. Caucasian skin also has more 
severe stratum corneum disruption, parakeratosis, and 
detached corneocytes. Both groups have the same degree of 
intra-epidermal spongiosis epidermal (granular and spinous 
layer) vesicle formation. 

The variability in human skin irritation responses 
sometimes creates difficulty in assessing the differences 
in skin reactivity between human subpopulations. There 
are conflicting results in studies comparing the sensitivity 
to irritants in Asian skin with that in Caucasian skin 
[32,43-46]. 


30 


4. Pigmentation and skin of color 


Dermis 

The dermis lies deep to the epidermis and is divided into two 
layers: the papillary and reticular dermis. The papillary 
dermis is tightly connected to the epidermis via the base¬ 
ment membrane at the dermoepidermal junction. The papil¬ 
lary dermis extends into the epidermis with finger-like 
projections, hence the name "papillary." The reticular dermis 
is a relatively avascular, dense, collagenous structure that 
also contains elastic tissue and glycosaminoglycans. The 
dermis is made up of collagen fibers, elastic fibers, and an 
interfibrillar gel of glycosaminoglycans, salt, and water. 
Collagen makes up 77% of the fat-free dry weight of skin 
and provides tensile strength. Collagen types I, II, V, and VI 
are found in the dermis. The elastic fiber network is inter¬ 
woven between the collagen bundles. 

There are differences between the dermis of white and 
black skin. The dermis of white skin is thinner and less 
compact than that of black skin [47]. In white skin, the 
papillary and reticular layers of the dermis are more distinct, 
contain larger collagen fiber bundles, and the fiber frag¬ 
ments are sparse. The dermis of black skin contains closely 
stacked, smaller collagen fiber bundles with a surrounding 
ground substance. The fiber fragments are more prominent 
in black skin than in white skin. While the quantity is similar 
in both black and white skin, the size of melanophages is 
larger in black skin. Also, the number of fibroblasts and 
lymphatic vessels are greater in black skin. The fibroblasts 
are larger, have more biosynthetic organelles, and are more 
multinucleated in black skin [6]. The lymphatic vessels are 
dilated and empty with surrounding elastic fibers [47]. No 
racial differences in the epidermal nerve fiber network have 
been observed using laser-scanning confocal microscopy, 
suggesting that there is no difference in sensory perception 
between races, as suggested by capsaicin response to C-fiber 
activation [48]. 

Skin extensibility is how stretchable the skin is. Elastic 
recovery is the time required for the skin to return to its 


original state after releasing the stretched skin. Skin elastic¬ 
ity is elastic recovery divided by extensibility. Studies that 
investigated skin extensibility, elastic recovery, and skin 
elasticity between races yield conflicting results [31,49]. It is 
likely that elastic recovery and extensibility vary by ana¬ 
tomic site, race, and age. 

Intrinsic skin aging in ethnic skin 

The majority of literature regarding facial aging features 
Caucasian patients. Facial aging is result of the combination 
of photodamage, fat atrophy, gravitational soft tissue redis¬ 
tribution, and bone remodeling. Figure 4.1 demonstrates the 
morphologic changes of the face caused by aging. The onset 
of morphologic aging appears in the upper face during the 
thirties and gradually progresses to the lower face and neck 
over the next several decades [50]. 

Early signs of facial aging occur in the periorbital region. 
In the late thirties, brow ptosis, upper eyelid skin laxity, and 
descent of the lateral portion of the eyebrow ("hooding") 
lead to excess skin of the upper eyelids. During the mid¬ 
forties, "bags" under the eyes result from weakening of the 
inferior orbital septum and prolapse of the underlying 
intraorbital fat. Lower eyelid fat prolapse may occur as early 
as the second decade in those with a familial predisposition. 
Photodamage produces periocular and brow rhytides [50]. 

Brow ptosis in African-Americans appears to occur to a 
lesser degree and in the forties opposed to the thirties com¬ 
pared to that in whites [51]. Prolapse of the lacrimal gland 
may masquerade as lateral upper eyelid fullness in African- 
Americans [52]. For Hispanics, the brow facial soft tissues 
sag at an earlier age [53]. In Asians, the descent of thick 
juxtabrow tissues in the lateral orbit coupled with the 
absences of a supratarsal fold may create a prematurely tired 
eye [50]. 

The midface show signs of aging during the forties. The 
malar soft tissue adjacent to the inferior orbital rim descends, 
accumulating as fullness along the nasolabial fold. The malar 


Figure 4.1 Morphologic signs of aging. (Adapted 
from figure by Cindy Luu. From Harris MO. (2006) 
Intrinsic skin aging in pigmented races. In: Haider 
RM, ed. Dermatology and Dermatological Therapy 
of Pigmented Skins. Taylor & Francis Group, 
pp. 197-209.) 


High brow- 

Prominent upper 
eyelid crease 

High protuberant 
cheek 

Soft nasolabial fold 
Full lips 

Smooth jawline 



Facial expression lines 
Low brow 

Excess upper eyelid skin 

Prominent fat pockets 
Lower lid hollowing 
'dark circles' 

Low cheek 

Prominent nasolabial fold 
Jowl 

Fat accumulation 


31 




















BASIC CONCEPTS Skin Physiology 


soft tissue atrophy and ptosis result in periorbital hollowing 
and tear trough deformity. Early aging is evident in indi¬ 
viduals of African, Asian, and Hispanic origin in the midface 
region more so than the upper or lower regions. Signs 
include tear trough deformity, infraorbital hollowing, malar 
fat ptosis, nasojugal groove prominence, and deepening of 
the nasolabial fold. This predisposition to midface aging is 
likely the result of the relationship of the eyes to the infraor¬ 
bital rim, basic midface skeletal morphology, and skin thick¬ 
ness [50]. 

The soft tissue of the lower face is supported in a youthful 
anatomic position by a series of retaining ligaments within 
the superficial musculo-aponeurotic system (SMAS) [54]. 
The SMAS is a discrete fascial layer that envolps the face and 
forms the basis for resuspending sagging facial tissues [14]. 
The SMAS fascia envelope maintains tension on facial 
muscles and offsets soft tissue sagging. In the late thirties, 
gradual ptosis of the SMAS and skin elastosis sets the stage 
for jowl formation. Accumulation of submandibular fat and 
a sagging submandibular gland may have a role in interrupt¬ 
ing the smooth contour of a youthful jaw line. Changes in 
the lower face lead to changes in the neck because the SMAS 
is anatomically continuous with the platysma muscle. 
Sagging of the SMAS-platysma unit and submandibular fat 
redistribution gradually blunts the junction between the jaw 
and neck. A "double chin" appears at any age as a result of 
cervicomental laxity with excess submental fat deposits. 
During the fifties, diastasis and hypertrophy of the anterior 
edge of the platysma muscle may produce vertical banding 
in the cervicomental area. During the sixth, seventh, and 
eighth decades, progressive soft tissue atrophy and bony 
remodeling of the maxilla and mandible create a relative 
excess of sagging skin, further exaggerating facial aging. 
Jowling is a sign of lower facial aging in black persons [50]. 
In some cases, a bony chin underprojection make create 
excess localized submental fatty deposits despite a smoothly 
contoured jaw line. However, in Asians, jowl formation may 
result from fat accumulation in the buccal space [50]. The 
"double chin" is more common in Caucasians under 40 
years of age than Asians of the same age group, but more 
common in Asians over 40 years of age because of redun¬ 
dant cervical skin [55]. 

Extrinsic aging (photoaging) of ethnic skin 

Sunlight is a major factor for the appearance of premature 
aging, independent of facial wrinkling, skin color, and skin 
elasticity. By the late forties, individuals with greater sun 
exposure appear older than those with less sun exposure. 
However, the perceived age of individuals in their late twen¬ 
ties is unaffected by sun exposure. Solar exposure greatly 
increases the total wrinkle length by the late forties. The 
extent of dermal degenerative change seen by the late forties 
correlates with premature aging. There is a high correlation 
between perceived age and facial wrinkles; perceived age 


and elastosis; and perceived age and the quantity of colla¬ 
gen. The grenz zone is a subepidermal band of normal 
dermis consisting of normal collagen fibers and thought to 
be a site of continual dermal repair. The grenz zone becomes 
visually apparent only after there is sufficient elastotic 
damage. With progressive elastosis, the grenz zone beomces 
thinner [56]. 

Histopathology 

Epidermis 

The absolute number of Langerhans cells vary from person 
to person but chronic sun exposure decreases their number 
or depletes them [57]. The severely sun-damaged skin has 
many vacuolated cells in the spinous layer, excessively vacu¬ 
olated basal keratinocytes and melnanocytes, cellular atypia, 
and loss of cellular polarity. Apoptosis in the basal layer is 
increased. A faulty stratum lucidum and horny layer result 
from intracellur vesicles in the cells of the basal and spinous 
layers (sunburn cells), apoptosis, and dyskeratosis. There is 
focal necrobiosis in the epidermis and dermis in sun-exposed 
skin. While histologic findings of photoaging in white sun- 
exposed skin include a distorted, swollen, and distinctly 
cellular stratum lucidum, the stratum lucidum of African- 
American sun-exposed skin remains compact and unaltered 
[6]. The stratum lucidum in black skin is not altered by 
sunlight exposure [6]. 

With age, the dermoepidermal junction becomes flattened 
with multiple zones of basal lamina and anchoring fibril 
reduplication. Microfibrils in the papillary dermis become 
more irregularly oriented. Compact elastic fibers show cystic 
changes and separation of skeleton fibers with age. The area 
occupied by the superficial vascular plexus in specimens of 
equal epidermal surface length decreases from the infant to 
young adult (21-29 years) to adult (39-52 years) age groups, 
then increased in the elderly adult (73-75 years) age group 
[58]. With the exception of the vascularity in the elderly 
adult group, the above features are similar to those seen in 
aging white skin, and suggest that chronologic aging in 
white and black skin is similar. Oxytalan fibers are found 
in the papillary dermis of sun-exposed skin of white indi¬ 
viduals in their twenties and early thirties but disappear in 
the forties. In black skin, the oxytalan fibers are still found 
in the dermis of individuals in their fifties. No solar elastosis 
is seen in specimens of black sun-exposed skin. Older black 
subjects have an increased number and thickness of elastic 
fibers that separate the collagenous fiber layer in the reticu¬ 
lar dermis. The single-stranded elastic fibers in individuals 
<50 years of age resemble braids in those >50 years of age. 
Finally, the sun-exposed skin of a 45-year-old light - 
complexioned black female shared the same amount and 
distribution of elastic fibers as those in white sun-exposed 
skin [6]. 

The grenz zone consists of small fibers oriented horizon¬ 
tally and replaces the papillary dermis. When elastotic mate- 


32 


4. Pigmentation and skin of color 


rial accumulates in the dermis, it crowds out all the 
collagenous fibers, which are resorbed. As the elastic mate¬ 
rial is resorbed, wisps of collagenous fibers form in its place. 
Widely spaced, larger collagenous fiber bundles lie between 
the waning elastotic masses. The total volume of the dermis 
gradually diminishes as the spaces between the remaining 
collagenous and elastic fibers are reduced. When the epider¬ 
mis rests directly on top of the horizontally oriented, 
medium-sized collagenous fiber bundles of the intermediate 
dermis, the dermis lacks a papillary and grenz zone and the 
dermis cannot sufficiently support the epidermis. As a result, 
the shrinking dermis crinkles and small wrinkles form. This 
may be the reason for the absence of a structural basis in 
secondary wrinkles and may explain why wrinkles flatten 
out when fluids are injected into the skin or when edema 
occurs [57]. 

Photoaging in skin of color has variable presentations. 
Wrinkling is not as common a manifestation of photoaging 
in black persons, South Asians, or darker complexioned 
Hispanics as in white persons because of the photoprotective 
effects of melanin. All racial groups are eventually subjected 
to photoaging. Within most racial groups, the lighter com¬ 
plexioned individuals show evidence of photodamaged skin. 
Caucasian skin has an earlier onset and greater skin wrin¬ 
kling and sagging signs than darker skin types. Visual pho¬ 
toaging assessments reveal that white skin has more severe 
fine lines, rhytides, laxity, and overall photodamage than 
African-American skin [41]. 

Photoaging is uncommon in black persons but is more 
often seen in African-Americans than in Africans or Afro- 
Caribbeans. The reason may be the heterogeneous mixture 
of African, Caucasian, and Native American ancestry often 
seen in African-Americans. In African-Americans, photoag¬ 
ing appears primarily in lighter complexioned individuals 
and may not be apparent until the late fifth or sixth decades 
of life [59]. Photoaging in this group appears as fine wrin¬ 
kling and mottled pigmentation. In spite of the photoprotec¬ 
tive effects of melanin, persons of skin of color are still prone 
to photoaging, but the reason is not completely known. 
Infrared radiation may also contribute to photodamage. 
There is evidence that chronic exposure to natural or artifi¬ 
cial heat sources can lead to histologic changes resembling 
that of UV-induced changes, such as elastosis and carcinoma 
[60]. The pigmentary manifestations of photoaging common 
in skin of color include seborrheic keratoses, actinic lentigi- 


nes, mottled hyperpigmentation, and solar-induced facial 
melasma [61]. However, African-American skin has greater 
dyspigmentation, with increased hyperpigmentation and 
uneveness of skin tone [40]. 


Hair 

There are two types of hair fibers: terminal and vellus. 
Terminal hair is found on the scalp and trunk. Vellus hair is 
fine and shorter and softer than terminal hair. The hair fiber 
grows from the epithelial follicle, which is an invagination 
of the epidermis from which the hair shaft develops via 
mitotic activity and into which sebaceous glands open. The 
hair follicle is one of the most proliferative cell types in the 
body and undergoes growth cycles. The cycles include 
anagen (active growth), catagen (regression), and telogen 
(rest). Each follicle follows a growth pattern independent of 
the rest. The hair follicle is lined by a cellular inner and outer 
root sheath of epidermal origin and is invested with a fibrous 
sheath derived from the dermis. Each hair fiber is made up 
of an outer cortex and a central medulla. Enclosing the hair 
shaft is a layer of overlapping keratinized scales, the hair 
cuticle that serves as protective layers. 

Racial differences in hair include the hair type, shape, and 
bulb. There are four types of hair: helical, spiral, straight, 
and wavy. The spectrum of curliness is displayed in Figure 
4.2. The vast majority of black persons have spiral hair [62]. 
The hair of black persons are naturally more brittle and more 
susceptible to breakage and spontaneous knotting than that 
of white persons. The kinky form of black hair, the weak 
intercellular cohesion between cortical cells, and the specific 
hair grooming practices among black persons account for the 
accentuation of these findings [62]. The shape of the hair is 
different between races: black hair has an elliptical shape, 
Asian hair is round-shaped straight hair, and Caucasian hair 
is intermediate [63,64]. The bulb determines the shape of 
the hair shaft, indicating a genetic difference in hair follicle 
structure [30]. The cross-section of black hair has a longer 
major axis, a flattened elliptical shape, and curved follicles. 
Asian hair has the largest cross-sectional area and Western 
European hair has the smallest [64,65]. Black persons have 
fewer elastic fibers anchoring the hair follicles to the dermis 
than white subjects. Melanosomes were in the outer root 
sheath and in the bulb of vellus hairs in black, but not in 


>»»««•«« 

Figure 4.2 The spectrum of curliness in human hair. (This figure was published in: Loussouarn G, Garcel A, Lozano I, Collaudin C, Porter Crystal, 
Panhard S, eta/. (2007) Worldwide diversity of hair curliness: a new method of assessment. Int J Dermatol 46 (Suppl 1), 2-6.) 


33 



BASIC CONCEPTS Skin Physiology 


white persons. Black hair also has more pigment and on 
microscopy has larger melanin granules than hair from 
light-skinned and Asian individuals. Similarities between 
white and black hair include: cuticle thickness, scale size and 
shape, and cortical cells [65]. 

While the curly nature of black hair is believed to result 
from the shape of the hair follicle [65], new research shows 
that the curliness of hair correlates with the distribution of 
cortical cells independent of ethnoracial origin [66]. Black 
hair follicles have a helical form, whereas the Asian follicle 


is completely straight and the Caucasian hair form is inter¬ 
mediate [65]. Mesocortical, orthocortical, and paracortical 
cells are the three cell types in the hair cortex. In straight 
hair, mesocortical cells predominate [66]. In wavy hair, the 
orthocortical and mesocortical cells are interlaced around 
paracortical cells. In tightly curled hair, the mesocortex dis¬ 
appears, making orthocortical cells the majority. Distinct 
cortical cells express the acidic hair keratin hHa8. Figure 4.3 
displays the distribution of hHa8 cells in straight, wavy, and 
tightly curled hair. Straight hair has a patchy but homoge- 



Figure 4.3 hHa8 hair keratin distribution in hair follicles. hHa8 pattern in (a) straight, (b) wavy, and (c) curly hair longitudinal sections. hHa8 pattern in 
(d) straight and (e) curly hair cross-sections. (From Thibaut eta/. (2007) Human hair keratin network and curvature. Int J Dermatol 46 (Suppl 1), 7-10.) 


34 









4. Pigmentation and skin of color 


nous pattern of positively charged hHa8 cells surrounding a 
core of negatively charged cells. As the degree of curl 
decreases, the hHa8 pattern becomes asymmetric, independ¬ 
ent of ethnic origin. In tightly curled hair, hHa8 accumulates 
on the concave side of the hair fiber and the medulla com¬ 
partment disappears. 

There are no differences in keratin types between hair 
from different races and no differences in amino acid com¬ 
position of hair from different races [67]. Among Caucasian, 
Asian, and Africans, there are no differences in the intimate 
structures of fibers, whereas geometry, mechanical proper¬ 
ties, and water swelling differed according to ethnic origin 
[68]. One study [69] in 1941 did find variation in the levels 
of some amino acids between black and white hair. Black 
subjects had significantly greater levels of tyrosine, pheny¬ 
lalanine, and ammonia in the hair, but were deficient in 
serine and threonine. 

The morphologic features of African hair were examined 
using the transmission and scanning electron microscopic 
(SEM) techniques in an unpublished study. The cuticle cells 
of African hair were compared with those of Caucasian hair. 
Two different electronic density layers were shown. The 
denser exocuticle is derived from the aggregation of protein 
granules that first appear when the scale cells leave the bulb 
region. The endocuticle is derived from the zone that con¬ 
tains the nucleus and cellular organites. The cuticle of 
Caucasian hair is usually 6-8 layers thick and constant in 
the hair perimeter, covering the entire length of each fiber. 
However, black hair has variable thickness; the ends of the 
minor axis of fibers are 6-8 layers thick, and the thickness 
diminishes to 1-2 layers at the ends of the major axis. The 
weakened endocuticle is subject to numerous fractures 
(Handjur C, Fiat, Huart M, Tang D, Leory F, unpublished 
data). 

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36 


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37 


Chapter 5: Sensitive skin and the somatosensory system 

Francis McGlone 1 and David Reilly 2 

Perception and Behaviour Group, Unilever Research & Development, Wirral, UK 
2 One Discover, Colworth Park, Sharnbrook, Bedford, UK 


BASIC CONCEPTS 

• The primary sensory modality subserving the body senses is collectively described as the somatosensory system, and comprises 
all those peripheral afferent nerve fibers, and specialized receptors, subserving cutaneous, and proprioceptive sensitivity. 

• Individuals with sensitive skin demonstrate heightened reactivity of the somatosensory system. 

• A separate set of neurons mediates itch and pain. The afferent neurons responsible for histamine-induced itch in humans are 
unmyelinated C-fibers. 

• Low threshold mechanoreceptors are responsible for the sensation of touch, a wide range of receptor systems code for 
temperature, and as the skin's integrity is critical for survival, there are an even larger number of sensory receptors and nerves 
that warn us of damage to the skin - the pain and itch systems. 


Introduction 

The primary sensory modality subserving the body senses is 
collectively described as the somatosensory system, and 
comprises all those peripheral afferent nerve fibers, and spe¬ 
cialized receptors, subserving cutaneous and proprioceptive 
sensitivity. The latter processes information about limb posi¬ 
tion and muscle forces which the central nervous system 
uses to monitor and control limb movements and, via 
elegant feedback and feedforward mechanisms, ensure that 
a planned action or movement is executed fluently. This 
chapter focuses on sensory inputs arising from the skin 
surface - cutaneous sensibility - and describes the neurobio- 
logic processes that enable the skin to "sense." Skin sensa¬ 
tions are multimodal and are classically described as sensing 
the three submodalities of touch, temperature, and pain. We 
also consider the growing evidence for a fourth submodality, 
present only in hairy skin, which is preferentially activated 
by slowly moving, low force, mechanical stimuli. 

This brief introduction to somatosensation starts with the 
discriminative touch system. Sensation enters the periphery 
via sensory axons that have their cell bodies sitting just 
outside the spinal cord in the dorsal root ganglia, with one 
ganglion for each spinal nerve root. Neurons are the build¬ 
ing blocks of the nervous system and somatosensory neurons 
are unique in that, unlike most neurons, the electrical signal 
does not pass through the cell body but the cell body sits off 
to one side, without dendrites. The signal passes directly 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


from the distal axon process to the proximal process which 
enters the dorsal half of the spinal cord, and immediately 
turns up the spinal cord forming a white matter column, the 
dorsal columns, which relay information to the first brain 
relay nucleus in the medulla. These axons are called the 
primary afferents, because they are the same axons that 
carry the signal into the spinal cord. Sensory input from the 
face does not enter the spinal cord, but instead enters the 
brainstem via the trigeminal nerve (one of the cranial 
nerves). Just as with inputs from the body, there are three 
modalities of touch, temperature, and pain, with each 
modality having different receptors traveling along different 
tracts projecting to different targets in the brainstem. Once 
the pathways synapse in the brainstem, they join the path¬ 
ways from the body on their way up to the thalamus and 
higher cortical structures. Sensory information arising from 
the skin is represented in the brain in the primary and sec¬ 
ondary somatosensory cortex, where the contralateral body 
surfaces are mapped in each hemisphere. 


Peripheral nervous system 

The skin is the most extensive and versatile organ of the 
body and in a fully grown adult covers a surface area 
approaching 2 m 2 . This surface is far more than a just a 
passive barrier. It contains in excess of 2 million sweat glands 
and 5 million hairs that may be either fine vellous types 
covering all surfaces, apart from the soles of the feet and the 
palms of the hands (glabrous skin), or over 100 000 of the 
coarser type found on the scalp. Evidence is also emerging 
that non-glabrous skin contains a system of nerves that code 
specifically for the pleasant properties of touch. Skin consists 


38 







5. Sensitive skin 


of an outer, waterproof, stratified squamous epithelium of 
ectodermal origin - the epidermis - plus an inner, thicker, 
supporting layer of connective tissue of mesodermal origin 
- the dermis. The thickness of this layer varies from 0.5 mm 
over the eyelid to >5.0mm over the palm and sole of the 
foot. 

Touch 

Of the three "classic" submodalities of the somatosensory 
system, discriminative touch subserves the perception of 
pressure, vibration, and texture and relies upon four differ¬ 
ent receptors in the digit skin: 

1 Meissner corpuscles; 

2 Pacinian corpuscles; 

3 Merkel disks; and 

4 Ruffini endings. 

These are collectively known as low threshold mech- 
anoreceptors (LTMs), a class of cutaneous receptors that are 
specialized to transduce mechanical forces impinging the 
skin into nerve impulses. The first two are classified as fast 
adapting (FA) as they only respond to the initial and final 
contact of a mechanical stimulus on the skin, and the 
second two are classified as slowly adapting (SA) as they 
continue firing during a constant mechanical stimulus. 
A further classification relates to the LTM's receptive field 
(RF; i.e. the surface area of skin to which they are sensitive). 
The RF is determined by the LTM's anatomic location 
within the skin, with those near the surface at the dermal- 
epidermal boundary, Meissner corpuscles and Merkel disks, 
having small RFs, and those lying deeper within the dermis, 
Pacinian corpuscles and Ruffini endings, having large RFs 
(Figure 5.1). 


Psychophysical procedures have been traditionally 
employed to study the sense of touch where differing fre¬ 
quencies of vibrotactile stimulation are used to quantify the 
response properties of this sensory system. Von Bekesy [1] 
was the first to use vibratory stimuli as an extension of his 
research interests in audition. In a typical experiment par¬ 
ticipants were asked to respond with a simple button-press 
when they could just detect the presence of a vibration 
presented to a digit, within one of two time periods. This 
two alternative force choice paradigm (2-AFC) provides 
a threshold-tuning curve, the slopes of which provide 
information about a particular class of LTM's response 
properties. 

Bolanowski et al. [2] proposed that there are four distinct 
psychophysical channels mediating tactile perception in the 
glabrous skin of the hand. Each psychophysically deter¬ 
mined channel is represented by one of the four anatomic 
end organs and nerve fiber subtypes, with frequencies in the 
40-500Hz range providing a sense of "vibration," transmit¬ 
ted by Pacinian corpuscles (PC channel or FAI); Meissner 
corpuscles being responsible for the sense of "flutter" in the 
2-40 Hz range (NPI channel or FAII); the sense of "pressure" 
being mediated by Merkel disks in the 0.4-2.0Hz range 
(NPIII or SAI); and Ruffini end organs producing a "buzzing" 
sensation in the 100-500 Hz range (NPII or SAII). 
Neurophysiologic studies have, by and large, supported this 
model, but there is still some way to go to link the anatomy 
with perception (Table 5.1). 

There have been relatively few studies of tactile sensitivity 
on hairy skin, the cat being the animal of choice for most of 
these studies. Mechanoreceptive afferents (A(l fibers) have 
been described that are analogous to those found in human 


Table 5.1 Main characteristics of primary sensory afferents innervating human skin. 


Class 

Modality 

Axonal diameter 
(pm) 

Conduction velocity 
(ms 1 ) 

Myelinated 

Aa 

Proprioceptors from 
muscles and tendons 

20 

120 

AP 

Low threshold 
mechanoreceptors 

10 

80 

A5 

Cold, noxious, thermal 

2.5 

12 

Unmyelinated 

C-pain 

Noxious, heat, thermal 

1 

<1 

C-tactile 

Light stroking, gentle touch 

1 

<1 

C-tutonomic 

Autonomic, sweat glands, 
vasculature 

1 

<1 


39 







Stratum corneum 

Stratum lucldum 
Stratum granulosum 

Melanocyte 
Stratum splnosum 

Stratum granulosum 
Lamina basilaris 
A Meissner's corpuscle 
• ■ ■ Merkel's disks 


} 


Stratum 

mucosum 


Pars papillris or 
Papillary dermis 
(loose connective tissue) 

Dermal nerve networks 
Ruffint endings 


Pars reticularis or 
• Reticular dermis 
- t dense connective tissue) 


Pacinian corpuscles 

Stratum subsutaneum 
Tela subcutanea 

Muscle, ligament, or bone 
Eccrine gland 


Epidermis 
Cuticle 
Scarf skin 


Dermis 
Cuticle 
True skin 


Hair shaft 


Melanocyte 

Erector 
pilorum 
muscle 1 


Sebaceous 
gland 


Hair follicle 
network 


(b) 



i 


Tactile pad 

Stratum corneum 
Stratum lucldum 
Stratum granulosum 
Stratum splnosum 
Stratum granulosum 
Lamina basilaris 
^Blood vessels 

. Pars papillris or 
Papillary dermis 
(loose connective tissue) 

Ruffint endings 

Dermal nerve networks 

Eccrine gland 


Apocrine gland 


Blood vessels 


Pars reticularis or 
* Reticular dermis 
dense connective tissue) 


Pacinian corpuscles 

Stratum subsutaneum 
Tela subcutanea 

Muscle, ligament, or bone 


Epidermis 
Cuticle 
Scarf skin 


Dermis 
Cuticle 
True skin 


Figure 5.1 A cross-sectional perspective of (a) glabrous and (b) hairy skin. (This figure was published with permission of the artist, R.T. Verrillo.) 









































5. Sensitive skin 


glabrous skin (FAI, FAII, SAI, SAII), and Essick and Edin [3] 
have described sensory fibers with these properties in human 
facial skin. The relationship between these sensory fibers 
and tactile perception is still uncertain. 

Sensory axons are classified according to their degree of 
myelination, the fatty sheath that surrounds the nerve fiber. 
The degree of myelination determines the speed with which 
the axon can conduct nerve impulses and hence the nerves 
conduction velocity. The largest and fastest axons are called 
Aa and include some of the proprioceptive neurons, such as 
the muscle stretch receptors. The second largest group, 
called A(3, includes all of the discriminative touch receptors 
being described here. Pain and temperature include the third 
and fourth groups, A5 and C-fibers. 

Electrophysiologic studies on single peripheral nerve 
fibers innervating the human hand have provided a gener¬ 
ally accepted model of touch that relates the four anatomi¬ 
cally defined types of cutaneous or subcutaneous sense 
organs to their neural response patterns [4]. The technique 
they employed is called microneurograpahy and involves 
inserting a fine tungsten microelectrode, tip diameter <3 pm, 
through the skin of the wrist and into the underlying median 
nerve which innervates the thumb and first two digits 
(Figure 3.2). 

Temperature 

The cutaneous somatosensory system detects changes in 
ambient temperature over an impressive range, initiated 


when thermal stimuli that differ from a homeostatic set- 
point excite temperature specific sensory nerves in the skin, 
and relay this information to the spinal cord and brain. It is 
important to recognize that these nerves code for tempera¬ 
ture change, not absolute temperature, as a thermometer 
does. The system does not have specialized receptor end 
organs such as those found with LTMs but uses free nerve 
endings throughout skin to sense changes in temperature. 
Within the innocuous thermal sensing range there are two 
populations of thermosensory fibers, one that respond to 
warmth (warm receptors) and one that responds to cold (cold 
receptors), and include fibers from the A5 and C range. 
Specific cutaneous cold and warm receptors have been 
defined as slowly conducting units that exhibit a steady-state 
discharge at constant skin temperature and a dynamic 
response to temperature changes [5,6]. Cold-specific and 
warm-specific receptors can be distinguished from nocicep¬ 
tors that respond to noxious low and high temperatures 
(<20°C and >45 °C) [7,8], and also from thermosensitive 
mechanoreceptors [5,9]. Standard medical textbooks describe 
the cutaneous cold sense in humans as being mediated by 
myelinated A-fibers with CVs in the range 12-30ms -1 [10], 
but recent work concludes that either human cold-specific 
afferent fibers are incompletely myelinated "BC" fibers, or 
else there are C as well as A cold fibers, with the C-fiber group 
contributing little to sensation (Figure 5.3) [11]. 

The free nerve endings for cold-sensitive or warm- 
sensitive nerve fibers are located just beneath the skin 


Adaptation 



Figure 5.2 The four types of low threshold mechanoreceptors in human 
glabrous skin are depicted. The four panels in the center show the nerve 
firing responses to a ramp and hold indentation and the frequency of 
occurrence (%) and putative morphologic correlate. The black dots in the 
left panel show the receptive fields of type I (top) and type II (bottom) 


afferents. The right panel shows the average density of type I (top) and 
type II (bottom) afferents with darker area depicting higher densities. 
(From Westling GK. (1986) Sensori-motor mechanisms during precision 
grip in man. Umea University medical dissertation. New Series 171, 
Umea, Sweden.) 


41 
































BASIC CONCEPTS Skin Physiology 



(b) 

Figure 5.3 Resting discharge of a C cold fiber at room temperature 
[11], (a) The resting discharge is suppressed by warming of the receptive 
field (RF) from 31 °C to 35°C. (b) From a holding temperature of 35°C f 
at which the unit is silent, activity is initiated by cooling the RF to 31 °C. 
(Time bar: 5s.) 

surface. The terminals of an individual temperature-sensitive 
fiber do not branch profusely or widely. Rather, the endings 
of each fiber form a small, discretely sensitive point, which 
is separate from the sensitive points of neighboring fibers. 
The total area of skin occupied by the receptor endings of a 
single temperature-sensitive nerve fiber is relatively small 
(approximately 1 mm in diameter), with the density of these 
thermosensitive points varying in different body regions. 
In most areas of the body there are 3-10 times as many 
cold-sensitive points as warm-sensitive points. It is well 
established from physiologic and psychologic testing that 
warm-sensitive and cold-sensitive fibers are distinctively 
different from one another in both structure and function. 

Pain 

Here we consider a system of peripheral sensory nerves that 
innervate all cutaneous structures and whose sole purpose 
is to protect the skin against potential or actual damage. 
These primary afferents include A5 and C-fibers which 
respond selectively and linearly to levels of thermal, mechan¬ 
ical, and chemical intensity/strength that are tissue-threat¬ 
ening. This encoding mechanism is termed nociception and 
describes the sensory process detecting any overt, or impend¬ 
ing, tissue damage. The term pain describes the perception 
of irritation, stinging, burning, soreness, or painful sensa¬ 
tions arising from the skin. It is important to recognize that 
the perception of pain not only depends on nociceptor input, 
but also on other processes and pathways giving information 
about emotional or contextual components. Pain is there¬ 
fore described in terms of an "experience" rather than just 
a simple sensation. There are again submodalties within the 


nociceptive system (A8 and C) subserving nociception. A5 
fibers are thin (1-5 pm), poorly myelinated axons of 
mechanical nociceptors, thermal receptors, and mechanore- 
ceptors with axon potential conduction velocities of approx¬ 
imately 12 ms -1 . C-fibers are very thin (<1 pm) unmyelinated 
slowly conducting axons of <1 ms -1 . Mechanical nociceptors 
are in the A5 range and possess receptive fields distributed 
as 5-20 small sensitive spots over an area approximately 
2-3 mm in diameter. In many cases activation of these spots 
depends upon stimuli intense enough to produce tissue 
damage, such as a pinprick. A5 units with a short latency 
response to intense thermal stimulation in the range 40- 
50 °C have been described as well as other units excited by 
heat after a long latency - usually with thresholds in excess 
of 50°C. 

Over 50% of the unmyelinated axons (C-fibers) of a 
peripheral nerve respond, not only to intense mechanical 
stimulation, but also to heat and noxious chemicals, and are 
therefore classified as polymodal nociceptors [12] or 
C-mechano-heat (CMH) nociceptors [13]. Receptive fields 
consist of single zones with distinct borders and in this 
respect they differ from A5 nociceptors that have multipoint 
fields. Innervation densities are high and responses have 
been reported to a number of irritant chemicals such as 
dilute acids, histamine, bradykinin, and capsaicin. Following 
inflammation some units can acquire responsiveness to 
stimuli to which they were previously unresponsive. 
Recruitment of these "silent nociceptors" implies spatial 
summation to the nociceptive afferent barrage at central 
levels, and may therefore contribute to primary hyperalgesia 
after chemical irritation and to secondary hyperalgesia as a 
consequence of central sensitization. 

Nociceptors do not show the kinds of adaptation response 
found with rapidly adapting LTMs (i.e. they fire continu¬ 
ously to tissue damage), but pain sensation may come and 
go and pain may be felt in the absence of any nociceptor 
discharge. They rely on chemical mediators around the 
nerve ending which are released from nerve terminals and 
skin cells in response to tissue damage. The axon terminals 
of nociceptive axons possess no specialized end organ struc¬ 
ture and for that reason are referred to as free nerve endings. 
This absence of any encapsulation renders them sensitive to 
chemical agents, both intrinsic and extrinsic, and inflamma¬ 
tory mediators released at a site of injury can initiate or 
modulate activity in surrounding nociceptors over an area 
of several millimeters leading to two kinds of sensory 
responses termed hyperalgesia - the phenomenon of 
increased sensitivity of damaged areas to painful stimuli. 
Primary hyperalgesia occurs within the damaged area; sec¬ 
ondary hyperalgesia occurs in undamaged tissues surround¬ 
ing this area. 

One further sensation mediated by afferent C-fibers is that 
of itch. The sensation of itch has, in the past, been thought 
to be generated by the weak activation of pain nerves, but 


42 




















5. Sensitive skin 


with the recent finding of primary afferent neurons in 
humans [14] and spinal projection neurons in cats [15], 
which have response properties that match those subjec¬ 
tively experienced after histamine application to the skin, it 
is now recognized that separate sets of neurons mediate itch 
and pain, and that the afferent neurons responsible for his¬ 
tamine-induced itch in humans are unmyelinated C-fibers. 
Until relatively recently it was thought that histamine was 
the final common mediator of itch, but clinical observations 
where itch can be induced mechanically, or is not found 
with an accompanying flare reaction, cannot be explained 
by histamine-sensitive pruriceptors leading to evidence for 
the existence of histamine-independent types of itch nerves 
[16] in which itch is generated without a flare reaction by 
cowhage spicules. As with the existence of multiple types of 
pain afferents, different classes of itch nerves are also likely 
to account for the various experiences of itch reported by 
patients [17]. 

Pleasure 

In recent years a growing body of evidence has been accu¬ 
mulating, from anatomic, psychophysical, electrophysio- 
logic, and neuroimaging studies, that a further submodality 
of afferent, slowly conducting, unmyelinated C-fibers exists 
in human hairy skin that are neither nociceptive nor pru¬ 
ritic, but that respond preferentially to low force, slowly 
moving mechanical stimuli. These nerve fibers have been 
classified as C-tactile afferents (CT-afferents) and were first 
described by Nordin [18] and Johansson et al. [19]. Evidence 
of a more general distribution of CT-afferents have subse¬ 
quently been found in the arm and the leg, but never in 
glabrous skin sites such as the palms of the hands or the 
soles of the feet [20]. It is well known that mechanorecep- 
tive innervation of the skin of many mammals is subserved 
by A and C afferents but until the observations of Nordin 
and Vallbo C-mechanoreceptive afferents in human skin 
appeared to be lacking entirely. 

The functional role of CT-afferents is not fully known, but 
their neurophysiologic response properties, fiber class, and 
slow conduction velocities preclude their role in any rapid 
mechanical discriminative or cognitive tasks, and point to a 
more limbic function, particularly the emotional aspects of 
tactile perception [21]. However, the central neural identi¬ 
fication of low-threshold C mechanoreceptors, responding 
specifically to light touch, and the assignment of a functional 
role in human skin has only recently been achieved. In a 
study on a unique patient lacking large myelinated Ab- 
fibers, it was discovered that activation of CT-afferents pro¬ 
duced a faint sensation of pleasant touch, and functional 
neuroimaging showed activation in the insular cortex but 
no activation the primary sensory cortex, identifying CT- 
afferents as a system for limbic touch that might underlie 
emotional, hormonal, and affiliative responses to skin-skin 
contacts between individuals engaged in grooming and 


bonding behaviors - pleasant touch [22]. If pain is elicited 
via sensory C- and A8-fibers then it is reasonable to specu¬ 
late that the same system may be alternatively modulated 
to deliver a sensation of pleasure. A study employing the 
pan-neuronal marker PGP9.5 and confocal laser microscopy 
has identified a population of free nerve endings in the 
epidermis that may be the putative anatomic substrate for 
this submodality [23]. 

Sympathetic nerves 

Although this chapter deals with sensory aspects of skin 
innervation it is important to acknowledge the role of a class 
of efferent (motor) nerves that innervate various skin struc¬ 
tures: (a) blood vessels; (b) cutaneous glands; and (c) unstri- 
ated muscle in the skin (e.g. the erectors of the hairs). In 
sensitive skin conditions, and some painful neuropathic 
states, sympathetic nerves have a role in exacerbating 
inflammation and irritation (for review see Roosterman 
etal. [24]). 


The central projections 

The submodalties of skin sensory receptors and nerves that 
convey information to the brain about mechanical, thermal, 
and painful stimulation of the skin are grouped into three 
different pathways in the spinal cord and project to different 
target areas in the brain. They differ in their receptors, path¬ 
ways, and targets, and also in the level of decussation (cross¬ 
ing over) within the CNS. Most sensory systems en route to 
the cerebral cortex decussate at some point, as projections 
are mapped contralaterally. The discriminative touch system 
crosses in the medulla, where the spinal cord joins the brain, 
the pain system crosses at the point of entry into the spinal 
cord. 

Spinal cord 

All the primary sensory neurons have their cell bodies situ¬ 
ated outside the spinal cord in the dorsal root ganglion, there 
being one ganglion for every spinal nerve root. 

Tactile primary afferents, or first order neurons, immedi¬ 
ately turn up the spinal cord towards the brain, ascending 
in the dorsal white matter and forming the dorsal columns. 
In a cross-section of the spinal cord at cervical levels, two 
separate tracts can be seen: the midline tracts comprise the 
gracile fasciculus conveying information from the lower half 
of the body (legs and trunk), and the outer tracts comprise 
the cuneate fasciculus conveying information from the 
upper half of the body (arms and trunk). At the medulla, 
situated at the top of spinal cord, the primary tactile afferents 
make their first synapse with second order neurons where 
fibers from each tract synapses in a nucleus of the same 
name - the gracile fasciculus axons synapse in the gracile 
nucleus, and the cuneate axons synapse in the cuneate 


43 



BASIC CONCEPTS Skin Physiology 


nucleus. The neurons receiving the synapse provide the 
secondary afferents and cross immediately to form a new 
tract on the contralateral side of the brainstem - the medial 
lemniscus - which ascends through the brainstem to the 
next relay station in the midbrain, the thalamus. 

As with the tactile system, pain and thermal primary 
afferents synapse ipsilaterally and then the secondary affer¬ 
ents cross, but the crossings occur at different levels. Pain 
and temperature afferents enter the dorsal horn of the spinal 
and synapse within one or two segments, forming the 
Lissauer tract as they do so. The dorsal horn is a radially 
laminar structure. The two types of pain fibers, C and A5, 
enter different layers of the dorsal horn. A5 fibers enter the 
posterior marginalis and the nucleus proprius, and synapse 
on a second set of neurons. These are the secondary affer¬ 
ents which will relay the signal to the thalamus. The second¬ 
ary afferents from both layers cross to the opposite side of 
the spinal cord and ascend in the spinothalamic tract. The 
C-fibers enter the substantia gelatinosa and synapse, but 
they do not synapse on secondary afferents. Instead they 
synapse on interneurons - neurons that do not project out 
of the immediate area but relay the signal to the secondary 
afferents in either the posterior marginalis or the nucleus 
proprius. The spinothalamic tract ascends the entire length 
of the cord and the entire brainstem and by the time it 
reaches the midbrain appears to be continuous with 
the medial lemniscus. These tracts enter the thalamus 
together. 

It is important to note that although the bulk of afferent 
input adheres to the plan outlined above there is a degree 
of mixing that goes on between the tracts. 

We have concentrated on somatosensory inputs from the 
body thus far, but as facial skin is often the source of sensi¬ 
tive reactions to topical applications, its peripheral and 
central anatomy and neurophysiology is briefly summarized 
here. The trigeminal nerve innervates all facial skin struc¬ 
tures (including the oral mucosa) and, just as with the spinal 
afferents, these neurons have their cell bodies outside of the 
CNS in the trigeminal ganglion with their proximal proc¬ 
esses entering the brainstem. Just as in the spinal cord, the 
three modalities of touch, temperature, and pain have dif¬ 
ferent receptors in the facial skin, travel along different 
tracts, and have different targets in the brainstem - the 
trigeminal nucleus - a relatively large structure that extends 
from the midbrain to the medulla. 

The large diameter (A(3) fibers enter directly into the main 
sensory nucleus of the trigeminal and, as with the somato¬ 
sensory neurons of the body, synapse and then decussate, 
the secondary afferents joining the medial lemniscus as it 
projects to the thalamus. The small diameter fibers convey¬ 
ing pain and temperature enter midbrain with the main Vth 
cranial nerve, but then descend down the brainstem to the 
caudal medulla where they synapse and cross. These 
descending axons form a tract, the spinal tract of V, and 


synapse in the spinal nucleus of V, so called because it 
reaches as far down as the upper cervical spinal cord. The 
spinal nucleus of V comprises three regions along its length: 
the subnucleus oralis, the subnucleus interpolaris, and the 
subnucleus caudalis. The secondary afferents from the sub¬ 
nucleus caudalis cross to the opposite side and join the 
spinothalamic tract where the somatosensory information 
from the face joins that from the body, entering the thala¬ 
mus in a separate nucleus, the ventroposterior medial (VPM) 
nucleus. 

Brain 

The third order thalamocortical afferents (from thalamus to 
cortex) travel up through the internal capsule to reach the 
primary somatosensory cortex, located in the post-central 
gyms, a fold of cortex just posterior to the central sulcus 
(Figure 5.4a). 

The thalamocortical afferents convey all of the signals, 
whether from the ventroposterior lateral (VPL) or VPM 
nucleus, to primary somatosensory cortex where the sensory 
information from all body surfaces is mapped in a somato- 
topic (body-mapped) manner [25], with the legs represented 
medially, at the top of the head, and the face represented 
laterally (Figure 5.4b). Within the cortex there are thought 
to be eight separate areas primarily subserving somatosensa- 
tion: primary somatosensory cortex, SI, comprised of four 
subregions (2, 1, 3a and 3b); secondary somatosensory 
cortex, SII, located along the superior bank of the lateral 
sulcus [26]; the insular cortex; and the posterior parietal 
cortex, areas 5 and 7b (Figure 5.5). 

As with studies of the peripheral nervous system, outlined 
above, the technique of microneurography has again been 
employed, in this case to study the relationship between skin 
sensory nerves and their central projections, as evidenced 
by the use of concurrent functional magnetic resonance 
imaging (fMRI). Microstimulation of individual LTM affer¬ 
ents, projecting to RFs on the digit, produces robust, focal, 
and orderly (somatotopic) hemodynamic (BOLD) responses 
in both primary and secondary somatosensory cortices [27]. 
It is expected that this technique will permit the study of 
many different topics in somatosensory neurophysiology, 
such as sampling from FA and SA mechanoreceptors and 
C-fibers with neighboring or overlapping RFs on the skin, 
quantifying their spatial and temporal profiles in response 
to electrical chemical and/or mechanical stimulation of the 
skin areas they innervate, as well as perceptual responses to 
microstimulation. 

Finally, the forward projections from these primary soma¬ 
tosensory areas to limbic and prefrontal structures has been 
studied with fMRI in order to understand the affective rep¬ 
resentations of skin stimulation for both pain and pleasure 
[28] and it is hoped that studies of this nature will help us 
to understand better the emotional aspects of both negative 
and positive skin sensations. 


44 


5. Sensitive skin 




Figure 5.4 (a) Outline of the somatosensory pathways from the digit tip to primary somatosensory cortex, via the dorsal column nuclei and the 
thalamus, (b) Penfield's somatosensory homunculus. Note the relative overrepresentation of the hands and lips, and the relative underrepresentation of 
the trunk and arms. 


Conclusions 



Lateral sulcus 


Central sulcus 

Intraparietal 

sulcus 


Figure 5.5 Cortical areas subserving somatosensation. Primary 
somatosensory cortex is located in the posterior bank of the central 
sulcus and the posterior gyrus and comprises areas 2, 1, 3a and 3b, 
secondary somatosensory cortex is located in the upper bank of the 
lateral sulcus with two further somatosensory regions in the posterior 
parietal cortex, areas 5 and 7b. 


In this chapter we describe the neural architecture of the 
skin senses, where it has been shown that the skin surfaces 
we groom when applying cosmetic agents are receptive to a 
wide variety of physicochemical forms of stimulation. Low 
threshold mechanoreceptors are responsible for the sensa¬ 
tion of touch, a wide range of receptor systems code for 
temperature, and, as the skin's integrity is critical for sur¬ 
vival, there are an even larger number of sensory receptors 
and nerves that warn us of damage to the skin - the pain 
and itch systems. In addition to this "classic" description of 
the skin senses, we also provide recent evidence for the 
existence of another skin receptor system which shares 
many of the same characteristics as the pain system with 
one important distinction - this system of sensory nerves is 
excited by low force, slowly moving tactile stimulation - 
such as that employed when grooming the body surfaces. 
This C-fiber-based system of peripheral cutaneous sensory 
nerves is therefore serving both a protective and hedonic 
role in body grooming behaviors. 


45 




















BASIC CONCEPTS Skin Physiology 


References 

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2 Bolanowski SJ, Gescheider GA, Verrillo RT, Checkosky CM. 
(1988) Four channels mediate the mechanical aspects of touch. 
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3 Essick GK, Edin BB. (1995) Receptor encoding of moving 
tactile stimuli in humans: the mean response of individual low- 
threshold mechanoreceptors to motion across the receptive 
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4 Valbo AB, Johansson RS. (1978) The tactile sensory innervation 
of the glabrous skin of the human hand. In: Gordon G, ed. Active 
Touch. New York: Pergammon, pp. 29-54. 

5 Hensel H, Boman KKA. (1960) Afferent impulses in cutaneous 
sensory nerves in human subjects. J Neurophysiol 23 , 564-78. 

6 Hensel H. (1973) Cutaneous thermoreceptors. In: Iggo A, ed. 
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7 Torebjork H. (1976) A new method for classification of C-unit 
activity in intact human skin nerves. In: Bonica JJ, Albe-Fessard 
D, eds. Advances in Pain Research and Therapy. New York: Raven, 
pp. 29-34. 

8 CamperoM, Serra J, Ochoa, JL. (1966) C-polymodal nociceptors 
activated by noxious low temperature in human skin. J Physiol 
497 , 565-72. 

9 Konietzny F. (1984) Peripheral neural correlates of temperature 
sensations in man. Hum Neurohiol 3 , 21-32. 

10 Darian-Smith I. (1984) Thermal sensibility. In: Darian-Smith I, 
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American Physiological Society, pp. 879-913. 

11 Campero M, Serra J, Bostock H, Ochoa JL. (2001) Slowly 
conducting afferents activated by innocuous low temperature in 
human skin. J Physiol 535 , 855-65. 

12 Besson M, Perl ER. (1969) Response of cutaneous sensory units 
with unmyelinated fibres to noxious stimuli. J Neurophysiol 32 , 
1025-43. 

13 Campbell JN, Raja SN, Cohen RH, Manning DC, Khan AA, 
Meyer RA. (1989) Peripheral neural mechanisms of nociception. 
In: Wall PD, Melzack R. eds. Textbook of Pain. Edinburgh: 
Churchill Livingstone, pp. 22-45. 

14 Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjork 
HE. (1997) Specific C-receptors for itch in human skin. J Neurosci 
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15 Andrew D, Craig AD. (2001) Spinothalamic lamina 1 neurons 
selectively sensitive to histamine: a central neural pathway for 
itch. Nat Neurosci 4 , 72-7. 


Ikoma A, Handwerker H, Miyachi Y, Schmelz M. (2005) 
Electrically evoked itch in humans. Pain 113 , 148-54. 
Yosipovitch G, Goon ATJ, Wee J, Chan YH, Zucker I, Goh CL. 
(2002) Itch characteristics in Chinese patients with atopic der¬ 
matitis using a new questionnaire for the assessment of pruritus. 
Int J Dermatol 41 , 212-6. 

Nordin M. (1990) Low threshold mechanoreceptive and 
nociceptive units with unmyelinated (C) fibres in the human 
supraorbital nerve. J Physiol 426 , 229-40. 

Johansson RS, Trulsson M, Olsson KA, Westberg KG. (1988) 
Mechanoreceptor activity from the human face and oral mucosa. 
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Valbo AB, Hagbarth IC-E, Torebjork HE, Wallin BG. (1979) 
Somatosensory, proprioceptive and sympathetic activity in 
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Essick G, James A, McGlone FP. (1999) Psychophysical assess¬ 
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Neuroreport 10 , 2083-7. 

Olausson H, Lamarre Y, Backlund H, Morin C, Wallin BG, Starck 
S, et al. (2002) Unmyelinated tactile afferents signal touch and 
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Reilly DM, Ferdinando D, Johnston C, Shaw C, Buchanan KD, 
Green M. (1997) The epidermal nerve fibre network: characteri¬ 
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assessment of racial variations. Br J Dermatol 137 , 163-70. 
Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff 
M. (2006) Neuronal control of skin function: the skin as a 
neuroimmunoendocrine organ. Physiol Rev S 6 , 1309-79. 
Maldjian JA, Gotschalk A, Patel RS, Detre, JA, Alsop DC. (1999) 
The sensory somatotopic map of the human hand demonstrated 
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Trulsson M, Francis ST, Kelly EF, Westling G, Bowtell R, 
McGlone FP. (2001) Cortical responses to single mechanorecep¬ 
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16 

17 

18 

19 

20 

21 

22 

23 

24 

25 

26 

27 

28 


46 


Chapter 6: Novel, compelling, non-invasive techniques for 
evaluating cosmetic products 

Thomas J. Stephens, 1 Christian Oresajo, 2 Robert Goodman, 1 Margarita 
Yatskayer, 2 and Paul Kavanaugh 1 

1 Thomas J. Stephens & Associates Inc., Dallas Research Center, Carrollton, TX, USA 
2 L'Oreal Research USA, Clark, NJ, USA 


BASIC CONCEPTS 

• Skin care products must be studied for safety and efficacy. 

• Non-invasive techniques were developed to assess the skin without a biopsy. 

• Non-invasive techniques are used to evaluate visual appearance, moisturization, barrier integrity, oiliness, elasticity, firmness, 
erythema, and skin color. 

• New photography techniques have been developed to detect changes in wrinkling of the face. 


Introduction 

Clinical trials for substantiation of cosmetic claims should be 
designed with good scientific rigor. In 1999, Rizer et al. [1] 
described an integrated, multidimensional approach for 
achieving this goal. The multistep process consisted of the 
following: careful subject selection, subject self-assessment 
of product performance, clinical grading, documentation 
photography, non-invasive bioengineering methods, and 
statistical analysis. 

Recently, the use of digital photography combined with 
image analysis has provided clinical investigators with a 
powerful new tool for quantifying improvements in wrin¬ 
kles, hyperpigmentation, pore size, skin tone, and other 
dermatologic conditions. 

Unlike past years, in which photographs of subjects were 
used solely to document clinical changes, use of photographs 
of subjects has moved beyond simple study documentation. 
This chapter introduces dermatologists, cosmetic surgeons, 
and clinical researchers to the cost-effective, non-invasive 
methods for substantiating cosmetic claims. It includes an 
overview of commonly used, non-invasive methods in cos¬ 
metic studies and a description of various types of high- 
resolution digital photography and their application for 
evaluating changes in skin. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Supporting cosmetic claims with 
bio-instrumentation 

Most scientists would agree that the use of non-invasive 
methods is an objective way for generating quantitative data 
about a product's performance on skin. Does this mean that 
data from non-invasive instruments provide conclusive 
evidence to support a cosmetic claim? 

Consider a topical lotion formulated to improve the 
appearance of facial wrinkles and moisturize skin. Now 
imagine that it is your responsibility to substantiate these 
claims in a clinical study using available non-invasive 
methods. Undoubtedly, you would choose proven methods 
such as replica profilometry to assess wrinkle changes and 
the Skicon™ (IBS Ltd., Tokyo, Japan) or Corneometer® 
(Courage & Khazaka Electronic GmbH, Koln, Germany) to 
assess changes in skin hydration. Would favorable data from 
both of these techniques provide conclusive evidence to 
support the claims? The answer may surprise you. 

In many cases, non-invasive methods are more useful in 
providing indirect lines of evidence to support a cosmetic 
claim. In clinical research this is called a secondary endpoint. 
A primary endpoint refers to the most meaningful result in 
a clinical trial. In the example above, the primary endpoints 
would be a visible improvement in the appearance of wrin¬ 
kles and reduction in the signs and symptoms of dry skin 
while the secondary endpoints would be improvements in 
wrinkle depth and high skin hydration values. 

The fact that many non-invasive methods are secondary 
endpoints does not diminish their importance in clinical 
research. Non-invasive methods often provide valuable 
information about the mechanism of action of a cosmetic 


47 







BASIC CONCEPTS Skin Physiology 


ingredient or cosmetic product on skin and a more reliable 
method to quantify improvements in skin. The use of color¬ 
imetry, a combination of digital photography and image 
analysis, is a much better method to quantify changes in 
skin erythema than by clinical examination, even though 
the human eye is very sensitive to color shifts. This tech¬ 
nique is more fully described at the end of this chapter. 


Commonly used non-invasive methods in 
cosmetic studies 

Approximately 90% or more of the cosmetic studies per¬ 
formed today are designed to support claims relating to 
improvements of fine lines or wrinkles, uneven skin pig¬ 
mentation associated with sun exposure and/or hormonal 
changes, enlarged pores, skin radiance, skin roughness, skin 
tone, and skin dryness. Table 6.1 provides a listing of com¬ 
monly used, non-invasive techniques that are used to help 
support these specific claims. For the reader who would like 
to learn more about these techniques or other non-invasive 
methods, there are a number of excellent books and articles 
available in the chapter's reference list [2-8]. 

Ideally, an investigator would like to see agreement 
between the clinical grading, non-invasive bio-instrumenta- 
tion measurements and subject self-perception question¬ 
naires. Occasionally, investigators obtain good concordance 
between clinical grading and self-perception questionnaires, 
but discordance with the non-invasive technique. 


Table 6.1 Commonly used bio-instruments and non-invasive 
procedures. 


Name 

Use 

NOVA Meter 

Moisturization 

SKICON 

Moisturization 

Corneometer 

Moisturization 

TEWA Meter 

Skin barrier function assessment 

Derma Lab 

Skin barrier function assessment 

Cutometer 

Firmness and elasticity 

ChromaMeter 

Skin tone, erythema, skin lightening, 
brightness 

Mexa meter 

Skin tone, erythema, skin lightening 

Sebumeter 

Oiliness (sebum) 

Sebutapes 

Oiliness 

D-Squames 

Scaling, exfoliation, and cell renewal 

Silicone Replica Impressions 

Skin texture, wrinkling 


Let us return to the example of the topical product 
designed to improve the appearance of wrinkles. It is not 
uncommon to see visible improvements in wrinkles during 
clinical grading while failing to detect the improvements 
using silicone replica profilometry. The discordance is not a 
result of grader error, but of limitation of the replica impres¬ 
sions to fully detect changes over the entire periocular area. 
Replica impressions are usually taken by spreading the 
unpolymerized replica material a few millimeters from the 
corner of the eye with the subject's eyes closed. This is nec¬ 
essary in order to prevent the replica material from running 
into the eye itself. If the grader makes his or her judgment 
based on the appearance of wrinkling in the areas adjacent 
to the corner of the eye as well as the area under the eye 
with the subject's eyes open, there is chance the grader 
might see improvements in wrinkling that might not be 
detected by the replica impression. Additionally, having the 
eyes closed while the impression is being taken can occa¬ 
sionally result in situations in which the subject squints, 
resulting in deeper, more pronounced wrinkles. The end 
result is a replica impression that detects more or deeper 
wrinkles. 

An alternative method, Raking Light Optical Profilometry 
(RLOP), which provides a newer, more novel approach for 
analyzing changes in wrinkling, is discussed below. The 
advantage of this technique is that the subject's eyes are 
open and the wrinkling appears in the same way as viewed 
by the clinical grader. 


Application of digital photography as a 
non-invasive technique for assessing skin 

The challenge for clinical documentation photography is 
twofold: to choose the best photographic technique relative 
to the aims of the study and to maximize consistency of the 
imaging at each clinic visit throughout the trial. The key to 
successful photography in clinical trials is the application 
of standardization, which includes the control subject's 
positioning, dress, lighting conditions, depth of field, 
background, and facial expression from visit to visit. The 
goal is to have images that accurately show treatment effects 
for use in medical and scientific journals. There is no place 
for misrepresenting clinical outcomes by changing viewing 
angles, altering lighting conditions, or having the subject 
apply facial makeup after using a product [9,10]. 

The first step to successful photography is to create the 
appropriate lighting and other photographic techniques spe¬ 
cific to the skin conditions of interest in the clinical study. 
A study involving a product designed to reduce the appear¬ 
ance of fine lines and wrinkles demands significantly differ¬ 
ent lighting than would trials involving acne, photodamaged 
skin, skin dryness or flakiness, scars, wound healing, postin- 
flammatory hyperpigmentation (PIH), or pseudofolliculitis 


48 







6. Evaluating cosmetic products 


barbae. In order to ensure a high degree of color consistency 
in photographic technique, the photographer should include 
color standard chips in each documentation image. Typically, 
these standards include small reference chips of white, 18% 
reflectance gray, black, red, green, and blue, as well as a 
millimeter scale for size confirmation. In addition, a more 
comprehensive color chart such as a ColorChecker® (X-Rite 
America Inc., Grand Rapids, MI, USA) should be photo¬ 
graphed under the exact standard lighting immediately 
before starting each photo visit. 

Equally crucial is the careful and detailed recording of 
all aspects of lighting, camera, and lens settings in order to 
achieve maximum consistency of documentation photo¬ 
graphs. Photographing each different photographic set-up 
provides more certainty that photographs at subsequent 
sessions are identical to the images made at baseline 
visit. 

Prior to photography, all makeup and jewelry must be 
removed, and hair kept clear of the subject's face by use of 
a neutral-color headband. Clothing should be covered by a 
gray or black cloth drape to prevent errors caused by color 
reflected from colored clothing. At each subsequent visit in 
the study, it is necessary to display the baseline image on 
the computer monitor for side-by-side comparison with that 
visit's photograph. Subject position, size, color, and lighting 
can thus be checked to make sure that changes in the skin 
are brought about by product effect, and are not artifacts 
caused by careless photographic technique. When the 
study is over, the sequence of images should look similar 
to a time-lapse video, with the only difference from one 
image to another being changes in the condition of the 
subject's skin. At Stephens & Associates, Inc. we have 


designed fully equipped photographic studios within our 
clinics so that subjects can be photographed under standard¬ 
ized conditions from visit to visit (Figure 6.1). These studios 
are manned by experienced medical photographers who 
have been trained in the basic science of conducting a 
clinical trial. While it is not possible for many clinics to have 
fully equipped studios with medical photographers in their 
office, there are other off-the-shelf alternatives which will 
allow them to control the quality of the images in clinical 
research. 

The VISIA, VISIA CR and VISIA CR2 are standardized 
camera systems that have been designed for use in clinical 
research. VISIA systems can be operated by individuals with 
little to no experience in photography. VISIA systems are 
composed of an oval-shaped plastic shell containing a digital 
camera and lighting system. Subject positioning is controlled 
by forehead and chin rests. VISIA contains proprietary 
software called VISIA Complexion Analysis Software System. 
The VISIA software system, developed by Procter and 
Gamble, counts the number of spots, pores, wrinkles, 
porphyrins, UV spots, red areas, and brown areas on the 
face of subjects. 

The VISIA CR® (Canfield Scientific Inc., Fairfield, NJ, 
USA) system has an advantage over the VISIA system 
in that quality of the images are usually better, because 
the VISIA CR system is equipped with higher resolution 
cameras than the standard or first generation VISIA 
system. At the time of writing, the Complexion Analysis 
Software (Figure 6.2) is not available on the VISIA CR or 
VISIA CR 2. A simpler software, using the Canfield RBx 
system, is currently compatible with the VISIA CR machines. 
Images taken with either system must be exported from the 



Figure 6.1 An example of a Stephens & Associates, Inc. photographic 
studio. The studio is equipped for taking photographs using standard 
lighting, parallel and polarized lighting, cross polarized lighting and 
raking light. 



Figure 6.2 An example of the data reporting for the VISIA Complexion 
Analysis Software. 


49 






BASIC CONCEPTS Skin Physiology 


camera for more detailed image analysis of spots, lines, wrin¬ 
kles, pores, and color changes. 

VISIA systems, while easy to use, have limitations in 
certain situations. The chin and head rests are sometimes 
too small for individuals with large faces, resulting in 
"jammed in" appearance. Additionally, it is difficult to see 
skin details such as acne lesions or PIH marks on images 
taken of subjects with Fitzpatrick skin types V and VI because 
of the close proximity of the subject's face to the camera and 
lighting system. Unlike viewing software provided by Nikon 
and Canon, VISIA does not allow images to be displayed 
from previous treatment visits and the baseline visit for a 
side-by-side image comparison. Therefore, it is difficult to 
make sure the head position and facial expressions are the 
same in all photographs. 


Review of terminology in clinical 
photography 

Individuals incorporating digital photography into a clinical 
trial are often faced with the difficult task of understating 
the vocabulary used by staff at clinical research organiza¬ 
tions (CROs). This section provides a concise description 
of commonly used terms and techniques in clinical 
photography. 

Visible light photography 

This refers to images made with unfiltered full-spectrum 
(white) light. It is the most common type of photography 
used in clinical trials. Proper positioning of the strobe flashes 
is a critical step for capturing various skin conditions in 
cosmetic clinical trials. Clinical studies involving evenness 
of color and skin tone require a more generalized, evenly 
distributed, visible lighting method while the imaging of 
fine lines, wrinkles, under eye bags, skin texture, and 
scaling is best achieved by placing the flashes in an off-axis 
direction. Off-axis lighting refers to lighting that is placed 
somewhat above and to the side to create small shadows 
and highlights on the skin thereby giving a three-dimen¬ 
sional quality to the image. Once the lighting conditions 
have been optimized, it is imperative that the photographer 
use documentation notes, setup photographs, light meter¬ 
ing and color charts to prevent lighting changes from visit 
to visit. 

Polarized photography 

This involves the placement of linear polarizing filters on 
both the lighting flash head(s) and in front of the lens of the 
digital camera. This allows the documentation of skin in two 
different ways [11]. 

The parallel-polarized lighting technique accentuates the 
reflection of light from the skin and tends to obscure fine 


topical detail because of strong reflections from the lighting 
source(s). Parallel-polarized light minimizes subsurface 
details, such as erythema and pigmentation, while allowing 
for enhanced viewing of the surface features of the skin, 
such as sweat, oily skin, and pores. 

The cross-polarized lighting technique involves fixing the 
transmission axis of the lens polarizer 90° to the axis of the 
lighting polarizer. This virtually eliminates the reflection of 
light (glare) from the surface of the skin and accentuates the 
appearance of inflammation from acne lesions, erythema, 
rosacea, and telangiectasia. Photodamaged skin becomes 
somewhat more apparent and some subsurface vascular 
features are made visible. Cross-polarized photography is 
useful for evaluating products designed to mitigate the 
appearance of dyschromic lesions, erythema, acne, and PIH 
resulting from acne. This technique is highly recommended 
for acne studies [12]. 

Examples of a parallel-polarized lighting technique and 
cross-polarized lighting technique can be found in Figure 
6.3. 

UV reflectance photography 

This is a technique designed to highlight or enhance hyper¬ 
pigmentation on the face. This is accomplished through fil¬ 
tering a flash source to only allow UV light to pass on to the 
subject's skin allowing visualization of subsurface melanin 
distribution. Figure 6.4 shows before and after UV reflect¬ 
ance photographs of a subject treated with a skin lightening 
product. A UV-blocking filter is placed in front of the lens 
of the digital camera. Note the improvement in the appear¬ 
ance and distribution of mottled and diffuse hyperpigmenta¬ 
tion in the photograph on the right. 

UV fluorescence photography 

This is primarily used to visualize the locations of 
Propionibacterium acnes in the pores of subjects with acne. 
Porphyrins produced by P. acnes exhibit an orange-red fluo¬ 
rescence under UVA light. Excitation of P. acnes on skin is 
achieved using a xenon flash lamp equipped with an UVA 
bandpass filter. The resulting fluorescence can be recorded 
using a high-resolution digital camera equipped with an UV 
barrier filter. An example of this technique can be found in 
Figure 6.3. 

Researchers have reported that UV fluorescence photog¬ 
raphy is a reliable, fast, and easy screening technique to 
demonstrate the suppressive effect of topical antibacterial 
agents on P. acnes [13]. Investigators need to be aware of a 
problem that can occur with using this technique to monitor 
P. acnes on the face. Many soaps, cosmetics, or sunscreen 
products contain quenching agents that can interfere with 
the accuracy of this imaging process. This can lead to an 
erroneous conclusion about the elimination of P. acnes from 
the face. 


50 



6. Evaluating cosmetic products 



Figure 6.4 Before and after UV 
reflectance photographs of a subject 
treated with a skin lightening product. 

(a) Ultraviolet reflectance at baseline. 

(b) Ultraviolet reflectance at 12 weeks. ( a ) 




Digital fluorescence photography has other applications in 
dermatologic research. The technique can be used to detect 
salicylic acid in the skin and follicles of subjects participating 
in claim studies, as well as follow the migration of sunscreen 
products over the surface of face. Following the migration 
of sunscreen products over the surface can help explain why 
some sunscreen products find their way into the eyes pro¬ 
ducing stinging, burning, and ocular discomfort. 

Guide photographs refer to photographs taken of mock 
subjects before the clinical trial begins to provide the sponsor 
and investigator with choices of techniques to best capture 
the dermatologic condition being studied. The chosen image 
becomes the guide, or standard, for photographing all sub¬ 
jects in the trial. 


Use of RLOP to detect improvements in 
periocular fine lines and wrinkles 

Optical profilometry refers to a technique in which photo¬ 
graphic images of silicone rubber impressions taken of facial 
skin can be analyzed for changes in lines and wrinkles. 
Grove et al. [14] reported that optical profilometry provides 
an element of objectivity that can complement clinical 
assessment in the study of agents that are useful for treating 
photodamaged skin. 

While no one would argue that optical profilometry is a 
time proven method for assessing textural changes, prepar¬ 
ing quality silicone replicas can be quite challenging even 


51 






BASIC CONCEPTS Skin Physiology 



Figure 6.5 Ultraviolet fluorescence technique. 


for veteran clinicians. Common problems include replica 
ring positioning errors, air bubbles in the replica impression, 
and controlling the polymerization process. Slight variations 
in temperature, humidity, and body temperature can 
produce unsuitable replica impressions. 

In an effort to reduce the frustration level associated with 
preparing silicone replicas, we began investigations into 
using high-resolution digital photographs for quantifying 
changes in fine line and wrinkles on the face. Off-axial light¬ 
ing, a common lighting technique used for clinical photog¬ 
raphy, could be used to create small shadows and highlights 
that could help define the surface texture of skin. Flash 
lighting can be placed above and at a 45 ° angle to the side 
of the face to create a three-dimensional effect of texture in 
a two-dimensional plane. The raw image files can be ana¬ 
lyzed for fine lines and wrinkles on the face. The term to 
describe this technique is RLOP. 

RLOP is designed to detect the number, length, width, and 
depth of horizontal wrinkles in the crow's feet area (coarse 
wrinkles) and the under eye area (fine lines). Wrinkles 
appear as dark lines on grayscale images. Deeper wrinkles 
appear darker because less light is present at the base of the 
wrinkle. An irregularly shaped area of interest is selected in 
the crow's feet area to avoid capturing the eyebrows or 
hairline, and a rectangular area of interest is used under the 
eye. Image Pro® v6 software (Media Cybernetics, Bethesda, 
MD, USA) is used for the analysis. A horizontal edge filter 
is used to locate the wrinkles and exclude any dark objects 
caused by hyperpigmentation or scars. Once the wrinkles 
are identified with the edge filter they are measured for size 
(length, width, and area) and grayscale density (where 


0 = black) on the original grayscale image. Once the data 
are collected a paired t-test is used to check for significant 
changes from baseline or between groups. 

As part of the validation process, RLOP has been included 
in several photoaging trials of cosmetic products involving 
several hundred subjects. The effectiveness of the products 
was evaluated using visual grading, digital photography with 
RLOP, bio-instrumentation, and subject self-assessment. The 
duration of these trials were typically 8 weeks, with clinic 
visits at 2, 4, and 8 weeks (Figure 6.6). 

RLOP technology complements and supports the results 
of clinical grading of fine line and wrinkles. RLOP appears 
to have several advantages over traditional optical 
profilometry. 

These advantages include: 

• RLOP can be performed on multiple sites on the face using 
a single digital photograph. 

• RLOP technology allows for precise location of the area 
of interest in each digital photograph through imaging 
software. 

• Digital images can be archived electronically for an indefi¬ 
nite period of time. 

• Results are expressed in meaningful units and 
endpoints. 

• The area of interest is significantly larger than can be 
captured in a replica impression. 

• RLOP can measure the full length of a wrinkle unlike 
traditional optical profilometry which limits the measured 
area to the size of the replica impression. 


A non-invasive method for assessing the 
antioxidant protection of topical 
formulations in humans 

It is well documented that the addition of antioxidants such 
as vitamins C, E, and A to skin care formulation can be 
beneficial in preventing and minimizing skin damage associ¬ 
ated with UV light [15-17]. Manufacturers often face a dif¬ 
ficult task when formulating with antioxidants, because 
they are easily destroyed or altered by oxidation which can 
occur during product manufacturing, filling, or storage. 

To address these concerns, Pinnell and colleagues devel¬ 
oped a human antioxidant assay which assesses the poten¬ 
tial of topical antioxidants to enter into the skin and provide 
adequate protection against UV damage generated by a solar 
simulator. Antioxidants provide protection from UVR- 
induced damage by diminishing or blocking the formation 
of reactive oxygen species which is clinically manifested by 
erythema [17]. 

The technique involves the open applications of antioxi¬ 
dant products and a vehicle control to the demarcated areas 
on the lower back of subjects for four consecutive days. On 
day 3 the minimal erythema dose (MED) is determined for 


52 




6. Evaluating cosmetic products 



Figure 6.6 Before and after photographs using Raking Light Optical Profilometry. Top row: Digital photographs from a trial of a subject before (a) and 
8 weeks after (b) treatment. Note the improvement in the appearance of wrinkling under the eye. Bottom row: Photographs shows the area of interest 
(AOI) in red. (c) Baseline, (d) Eight weeks after. The AOIs were precisely located in each digital image by using anatomic landmarks as anchors. 


each subject. This is the dose of UV light that produces slight 
redness on fair-skinned individuals. 

On day 4, the demarcated sites treated with the antioxi¬ 
dant product, vehicle control, and an untreated site receive 
solar-simulated UV irritation of 1-5X MED at IX MED inter¬ 
vals. On day 5, digital images are taken and the investigator 
has the option of collecting punch biopsies at the treatment 
sites and analyzing the tissues for multiple bio-markers such 
as thymine dimers, interleukins, metaloproteins, Langerhans 
cells (CDla), p53, and sunburn cells [13,14]. 

Figure 6.7 shows a pattern of UV responses for a site 
treated with an antioxidant and a site treated with a vehicle 
control. Using macro-programs written in Image Pro soft¬ 
ware, it is possible to determine accurately the a* (degree of 
redness according to the CIE color standard) of each spot 


and to calculate a protection factor for the antioxidant 
product relative to vehicle control treated site (Table 6.2). 

Using this technique, Pinnell and associates have been 
able to formulate a third generation antioxidant product that 
provides protection against the damaging effects of UV light. 
The formulation containing 15% ascorbic acid, 1% alfa- 
tocopherol, and 0.5% ferulic acid was found to be effective 
in reducing thymine dimers known to be associated with 
skin cancer [18,19]. 


Conclusions 

Photography and other non-invasive techniques are impor¬ 
tant to assess the efficacy and safety of cosmetic products. 


53 







BASIC CONCEPTS Skin Physiology 


Erythema 


Control 


Test material 



1 

2 

3 

xMED 

Table 6.2 Results of theorectical antioxidant protection factor 
calculations. 


Increase from 
unexposed 
(adjusted for MED) 

Protection 

factor (%) 

No treatment (control) 

10.50 

0.0 

Antioxidant 

6.30 

60.0 

Vehicle control 

0.53 

2.6 


MED, minimal erythema dose. 


Often, the non-invasive assessments provide confirmation 
of the expert grader assessments. It is reassuring to see con¬ 
sistency within the data set to confirm a positive effect of 
cosmetics and skin care products. This validation technique 
is necessary to truly evaluate products. This chapter presents 
several cutaneous research tools. 

References 

1 Rizer RL, Sigler ML, Miller DL. (1999) Evaluating performance 
benefits of conditioning formulations on human skin. In: 
Schueller R, Romanowski P, eds. Conditioning Agents for Hair and 
Skin. pp. 345-51. 

2 Berardesca E. (1997) EEMCO guidance for the assessment of 
stratum corneum hydration: electrical methods. Skin Res Technol 
3, 126-32. 

3 Eisner P, Barel AO, Berardesca B, Gabard B, Serup J. (1998) Skin 
Bioengineering. Basel; New York: Karger. 

4 Flosh PJ, Kligman AM. (1993) Non-invasive Methods for the 
Quantification of Skin Functions. Springier-Verlag. 

5 Serup J, Jemec GBE. (1995) Handbook of Non-invasive Method and 
the Skin. Boca Raton, FL: CRC Press. 

6 Eisner P, Berardecsa E, Wilhelm KP, Maibach HI. (2006) 
Bioengineering of the Skin: Skin Biomechanics. Boca Raton, FL: CRC 
Press. 


Figure 6.7 Pattern of UV responses for a 
site treated with an antioxidant and a site 
treated with a vehicle control. 


7 Eisner P, Berardesca E, Wilhelm KP. (2006) Bioengineering of the 
Skin: Skin Imaging and Analysis , 2nd edn. Informaword. 

8 Eisner P, Berardecsa E, Wilhelm KP, Maibach HI. (1995) 
Bioengineering of the Skin: Methods and Instrumentation. Taylor & 
Francis. 

9 Stack LB, Storrow AB, Morris MA, Patton DR. (1999) Handbook 
of Medical7 Photography Philadelphia, PA: Hanley & Belfus, pp. 
15-20. 

10 Ratner D, Thomas CO, Bickers D. (1999) The use of digital 
photography in dermatology. J Am Acad Dermatol 41, 749-56. 

11 Phillips SB, Kollias N, Gillies R, Muccini A, Drake LA. (1997) 
Polarized light photography enhances visualization of inflamma¬ 
tory lesions of acne vulgaris. J Am Acad Dermatol 37, 948-52. 

12 Rizova E, Kligman A. (2001) New photograqphic technique 
for clinical evalution of acne. J Eur Acad Dermatol Venereol 15 
(Suppl 3), 13-8. 

13 Pagnoni A, Kilgman AM, Kollias N, Goldberg S, Stoudemeyer T. 
(1999) Digital fluorescence photography can assess the suppres¬ 
sive effect of benzoyl peroxide on Propionibacterium acnes. J Am 
Acad Dermatol 41, 710-6. 

14 Grove GL, Grove MJ, Leyden JJ. (1989) Optical profilometry: 
an objective method for quantification of facial wrinkles. J Am 
Acad Dermatol 21, 631-7. 

15 Rabe JH, Mamelak AJ, EcElgunn JS, Morrison WL, Sauder DN. 
(2006) Photoaging: mechanisms and repair. J Am Acad Dermatol 
55, 1-19. 

16 Dreher F, Denig N, Gabard B, Schwindt Da, Maibach MI. (1999) 
Effect of topical antioxidants on UV-induced erythema forma¬ 
tion when administered after exposure. Dermatology 198, 52-5. 

17 Pinnell, SR (2003). Cutaneous photodamage, oxidative stress 
and topical antioxidant protection. J Am Acad Dermatol 48(1), 
1-19. 

18 Murray JC, Burch JA, Streilein RD, Iannacchione MA, Hall RP, 
Pinnell SR. (2008) atopical antioxidant solution containing 
vitamins C and E stabilized by ferulic acid provides protection 
for human skin against damage caused by ultraviolet irradiation. 
J Am Acad Dermatol 59, 418-25. 

19 Oresajo C, Stephens T, Hino PD, Law RM, Yatskayer M, Foltis 
P, etal. (2008) Protective effects of a topiocal antioxidant mixture 
containing vitamin C, and phloretin against ultraviolet-induced 
photodamage in human skin. J Cosmet Dermatol 7, 290-7. 


54 






Chapter 7: Contact dermatitis and topical agents 

David E. Cohen and Aieska de Souza 

New York University School of Medicine Department of Dermatology, New York, NY, USA 


BASIC CONCEPTS 

• Hypersensitivity reactions can occur in response to topical agents. 

• Adverse reactions can be characterized by irritant contact dermatitis and allergtic contact dermatitis. 

• Patch testing is a reliable method for determining the etiology of adverse reactions to topical products. 

• Treatment of hypersensitivity reactions involves prompt recognition with identification and withdrawal of the offending agent. 


Introduction 

Topical cosmetic medications, cosmeceuticals, and mini¬ 
mally invasive procedures have always had an important 
role in dermatologic practice, but recent advances have led 
to a tremendous expansion in the repertory of treatment 
modalities available. In addition, the use of over-the-counter 
cosmetics is rising worldwide, along with potential exposure 
to irritants and allergenic substances [1]. Adverse skin reac¬ 
tions to cosmetics include irritant contact dermatitis, allergic 
contact dermatitis, contact urticaria, and foreign body reac¬ 
tions [2]. The clinician should be able to diagnose these 
cases, prescribe the correct treatment, and - most impor¬ 
tantly - identify the causative agent. Most of these reactions 
are treatable without sequelae once the offending agent is 
identified and avoided [2]. 

Approximately 15 million Americans have been diag¬ 
nosed with contact dermatitis [2]. The US Food and Drug 
Administration (FDA) regulations on cosmetics are based in 
two important laws: the Federal Food, Drug, and Cosmetic 
Act (FD&C) which prohibits the marketing of adulterated or 
misbranded cosmetics, and the Fair Packaging and Labeling 
Act (FPLA) which states that improperly labeled or decep¬ 
tively packaged products are subject to regulatory action [3]. 
Ingredient labeling is mandatory in the USA and Europe, 
and compounds are listed in descending order of amount 
using the nomenclature format of the International Cosmetic 
Ingredient Dictionary [4,5]. However, with the exception of 
color additives, cosmetic products and ingredients are not 
subjected to FDA premarket approval and manufacturers' 
reporting of adverse reactions is a voluntary process [3]. In 
order to review the safety of the cosmetic ingredients, the 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Cosmetic, Toiletries and Fragrance Association (CTFA) spon¬ 
sors the Cosmetic Ingredient Review (CIR). Reactions to 
cosmetics can manifest in a wide range of clinical signs, 
therefore it is important for the clinician to be familiar with 
the diversity of those presentations to enable prompt diag¬ 
nosis and treatment. 


Hypersensitivity reactions: 
pathophysiology and clinical presentations 

Irritant contact dermatitis 

Most skin reactions to cosmetics are classified as irritant 
contact dermatitis [4]. Irritant contact dermatitis is caused 
by endogenous and environmental elements and it is defined 
as local inflammation that is not initially mediated by the 
immune system. Predisposing factors for the development 
of irritant dermatitis included the presence of a less effective 
stratum corneum, either from anatomic conditions (face, 
eyelids) or secondary to endogenous disorders, such as 
atopic dermatitis. The severity of the dermatitis depends on 
the amount and strength of the agent, and length and fre¬ 
quency of exposure. Repetitive exposures even to mild 
agents, such as soaps and detergents, will often result in 
irritant dermatitis. In addition, harsh scrubbing with 
mechanical assistance (brushes, synthetic sponges, or cos¬ 
metics containing microabrasive spheres) increases the risk 
for irritation. Psychiatric disorders, leading to compulsive 
repetitive behaviors of self-cleaning and handwashing, can 
sometimes be overlooked and a complete patient history 
must include cleaning habits, occupation, and a detailed list 
of all products used on both a daily and occasional basis. 

Allergic contact dermatitis 

Allergic dermatitis constitutes at least 10-20% of all cases of 
contact dermatitis and represents a true delayed-type (type 
IV) immune reaction. Previous exposure and sensitization 


55 







BASIC CONCEPTS Skin Physiology 


to the agent is necessary [2]. Chemical agents act as haptens, 
which are small electrophilic molecules that bind to carrier 
proteins and penetrate into the skin. HLA-DR or class II 
antigens act as the binding site in the surface of the antigen- 
presenting cells (APCs). These epidermal dentritic cells digest 
the allergen complex and display the antigenic site on their 
cell surfaces for presentation to T lymphocytes. If the indi¬ 
vidual has the genetic susceptibility to that allergen, clonal 
proliferation of T cells starts with the production of cytokines, 
further stimulating migration of inflammatory cells and 
keratinocyte proliferation. 

Clinical distinction between irritant and allergic dermatitis 
can be challenging because both conditions manifest as 
eczematous reactions, ranging from mild erythema and 
scale with minimal itch to vesicular, bullous, and indurated 
plaques that are highly pruritic. Furthermore, the two 
conditions can be superimposed, because an irritated and 
broken epidermal barrier can facilitate the absorption of 
haptens and elicit an immune response in susceptible 
individuals. 

Contact urticaria 

Contact urticaria syndrome is divided into immunologic and 
non-immunologic subtypes. Non-immunologic contact urti¬ 
caria is the most common form and occurs in the absence 
of previous exposure. Localized wheals appear within 30-60 
minutes after exposure and are not followed by systemic 
symptoms. Allergic contact urticaria is an immediate-type 
(type I) hypersensitivity reaction and occurs in sensitized 
individuals within minutes to hours following the exposure 
to the allergen. The binding between allergens and immu¬ 
noglobulin E (IgE) triggers mast cell degranulation and con¬ 
sequent release of inflammatory products, such as histamine, 
prostaglandins, leukotrienes, and cytokines. As a conse¬ 
quence, individuals experience erythema, swelling, and pru¬ 
ritus which may be localized (wheals and fares) or generalized 
(angioedema, conjunctivitis, bronchoconstriction, hypoten¬ 
sion). Severe reactions may be fatal. 

Foreign body reactions 

Gel fillers are a group of exogenous substances used for soft 
tissue augmentation. Their mechanism of action is the addi¬ 
tion of volume per se once injected and also the production 
of a collagen matrix. Fillers are supposed to be inert materi¬ 
als but the degree of the response elicited varies according 
to the material and the technique used, as well as the host 
immunologic pattern of reaction. 

The normal initial host response to foreign body implanta¬ 
tion is the formation of a blood-based matrix on and around 
the biomaterial, called the provisional matrix. The tissue 
injury may also lead to activation of the innate immune 
response and thrombus formation. The provisional matrix is 
rich in mitogens, chemoattractants, growth factors, and 
cytokines, proving an excellent medium both for wound 


healing and foreign body reaction. Acute inflammation is 
characterized by the presence of neutrophils, mast cell 
degranulation, and fibrinogen adsorption. The degree of the 
inflammation is highly dependent upon the injury pro¬ 
duced, the site of injection, the material used, and the extent 
of the provisional matrix formed. The acute phase generally 
resolves within 1 week, and can be followed by chronic 
phase inflammatory response, which is characterized by the 
presence of monocytes, lymphocytes, and plasma cells. After 
resolution of acute and chronic phases of inflammation, a 
granulation tissue can be identified, rich in macrophages and 
fibroblasts which act to produce neovascularization and new 
healing tissue [6]. Prolonged duration of the inflammatory 
phase (i.e. longer than 3 weeks) should prompt an investiga¬ 
tion to rule out complications, such as infection, allergic 
reaction, gel migration, abscesses formation, or granuloma¬ 
tous reaction. Foreign body granulomatous reactions with 
deleterious consequences have been previously described 
with the use of silicon, bovine collagen, hyaluronic acid, and 
other fillers [2,7-10]. 


Common allergens 

Irritants 

In the clinical setting, irritant substances are used for the 
purpose of selectively destroying the damaged superficial 
layers of the skin, and the depth of penetration is correlated 
with the agent used, concentration, and time of exposure. 
Examples of "peeling" agents include retinoic, glycolic, and 
salicylic acids, resorcinol, trichloroacetic acid, and phenol. 
Undesirable irritant reactions are commonly seen with daily 
use of topical retinoids, leading to erythema and fine scaling, 
which tend to improve with time. 

A wide variety of substances may act as irritants when 
sufficient exposure in time and/or concentration is ensured 
(Table 7.1). Mechanical, chemical, and environmental 
factors can act alone or in combination to produce irritation 
in the skin. Mechanical factors include cosmetic procedures 
(shaving, waxing, laser therapy, dermoabrasion), habits 
(excessive rubbing of the skin with soaps, scrubs, usage of 
tight clothes or shoes, intense exercise), occupational expo¬ 
sure (latex gloves, microtrauma of the skin). Wet work (i.e. 
exposure of the skin to liquid), use of occlusive gloves for 
longer than 2 hours per day or frequent hand cleaning is 
one of the most common and important skin irritants [11]. 
Professions at risk include hairdressers, healthcare workers, 
and food handlers. 

Almost all chemicals have the potential to cause skin irri¬ 
tation. The list of the chemical compounds capable of pro¬ 
ducing irritation of the skin is extensive and largely 
dependent on the concentration, volume, and time of expo¬ 
sure. Some substances are considered universal irritants, for 
example, strong acids (hydrofluoric, hydrochloric, sulfuric. 


56 



7. Contact dermatitis and topical agents 


Table 7.1 List of common skin irritants: mechanic, chemical, and environmental factors known to cause skin irritation. The agents can act alone or 
in combination to produce contact dermatitis, therefore recognition of all factors involved is crucial for proper management of patients. 

Mechanic 

Chemical 

Environmental 

Shaving, waxing, laser treatment 

Soaps 

Excessive heat or sun exposure, sunburn 

Dermoabrasion 

Detergents 

Food allergies 

Rubbing of the skin (e.g. when using 
a soap or scrubbing) 

Surfactants (cocamidopropyl betaine*) 

Saunas and jacuzzis (chlorine*) 

Friction and/or occlusion (tight clothes, 
certain fabrics: wool, synthetic fibers) 

Chemical peelings 

Extreme cold and windburn 

Latex gloves 

Alcohol 

Stress 

Intense exercise 

Fragrances and color additives (musk*) 

Dry air 

Microtrauma 

Preservatives (formaldehydes releasing substances: 
Quaternium 15*, imidazolidinyl urea, DMDM Hydantoin) 

Hot and/or prolonged showers 

Pressure 

Sunscreens (para-aminobenzoic acid*) 

Spicy foods, peppers, condiments 

Wet work 

Bleaches and whitening agents 

Water 

*Most common chemical compounds involved. 


nitric acids) and strong caustics (sodium hydroxide, potas¬ 
sium hydroxide) produce severe burns even in brief and 
small exposures. Solvents, including alcohol, turpentine, 
ketones, and xylene, remove lipids from the skin, producing 
direct irritation and allowing other irritants, such as soap 
and water, to produce more damage on the exposed skin. 
Inappropriate skin cleansing with solvents to remove grease, 
paints, or oils is a common cause of skin irritation. Soaps are 
alkali substances and may produce irritation by disrupting 
the skin barrier; in contrast, cleansing agents with a pH of 
approximately 5.5 and alcohol-based hand-cleansing gels 
are less aggressive and should be preferred for sensitive skin. 

Environmental elements may render the skin more sus¬ 
ceptible to cutaneous irritants, and include dry air, extremes 
of temperature (cold, heat), or important weather varia¬ 
tions. Food allergies may cause urticarial reactions; spicy 
foods and condiments may cause lip and perioral irritant 
dermatitis. Prolonged exposure to water can cause macera¬ 
tion and desiccation of the skin. 

Acneiform eruptions refer to the presence of comedones, 
papules, pustules, and nodular cysts. Follicular plugging has 
been noticed secondary to the use of isopropyl myristate, an 
emollient and lubricant used in shaving lotions, shampoos, 
oils, and deodorants. Sodium lauryl sulfate (SLS) is a sur¬ 
factant found in many topical medications, particularly for 
acne, and is a classic experimental cutaneous irritant. 
Pustular eruptions secondary to SLS have also been 
described. Bergamot oil (5-methoxypsoralen) induced pho¬ 
totoxic reactions in the past and it has subsequently been 
removed from the formulations of cosmetics. Photosensitivity 
reactions caused by topical retinoid preparations are common 


and patients should be advised to use sunscreens and avoid 
sun exposure during treatment. 

Subjective irritation, described as a tingling, burning, 
stinging, or itching sensation without visible skin alteration 
is commonly observed with topical medications. Propylene 
glycol, hydroxy acids, and ethanol are capable of eliciting 
sensory irritation in susceptible individuals. Commonly used 
medications such as benzoic acid, azelaic acid, lactic acid, 
benzoil peroxide, mequinol, and tretinoin may have sensory 
irritation as a side effect. Sorbic acid is an organic compound 
used as a preservative in concentrations up to 0.2% in foods, 
cosmetics, and drugs. Subjective irritation has been demon¬ 
strated with 0.5% sorbic acid and to 1% benzoic acid in 
susceptible individuals [12]. 

"Sensitive skin" or cosmetic intolerance syndrome is a 
condition of cutaneous hyperreactivity secondary to sub¬ 
stances that are not defined as irritants [13]. The condition 
encompasses a complex combination of objective and sub¬ 
jective irritative symptoms and may coexist with hidden 
allergic processes, urticarial reactions, and/or photodermati¬ 
tis. Endogenous causes include seborrheic dermatitis, pso¬ 
riasis, rosacea/perioral dermatitis, atopic dermatitis, and 
body dysmorphobia. Elimination of all cosmetic products for 
a prolonged period of time (6-12 months) followed by slow 
reintroduction (a new products every 2-3 weeks) is helpful 
when managing these cases. 

Contact urticaria 

Cinnamic acid is a white crystalline substance, slightly 
soluble in water, which is obtained from oil of cinnamon, 
or from balsams such as storax. Its primary use is in the 


57 





BASIC CONCEPTS Skin Physiology 


manufacturing of the methyl, ethyl, and benzyl esters for 
the perfume industry, producing the "honey, fruit" odor. 
Type I non-immunologic reactions can be triggered by fra¬ 
grances that contain cinnamic acid and cinnamal. 

Immunologic type I reactions can be triggered in suscep¬ 
tible individuals by parabens (preservatives), henna, and 
ammonium persulfate (oxidizing agent), leading to systemic 
symptoms and potentially fatal reactions [4]. Contact urti¬ 
caria to latex is triggered by exposure to the proteins derived 
from Hevea brasiliensis tree. Risk factors include the presence 
of spina bifida, genitourinary tract abnormalities, previous 
contact to latex (from multiple surgical procedures, or occu¬ 
pational exposure) hand dermatitis, atopy, and specific food 
allergies (avocado, banana, chestnut, potato, tomato, kiwi, 
pineapple, papaya, eggplant, melon, passion fruit, mango, 
wheat, and cherimoya). 

Allergic reactions 

Fragrances 

Allergic reactions to fragrances affect at least 1% of the 
population. The distribution of the eruption can be restricted 
to the areas of application (face, neck, hands, axillae) or it 
can present as generalized dermatitis. Products containing 
scents are ubiquitous and include cosmetics and toiletries, 
cleansers, and household goods. Common sensitizers are 
balsam of Peru, cinnamal, fragrance mix (eugenol, isoeug- 
enol, oak moss absolute, geraniol, cinnamal, alfa-amyl cin¬ 
namic aldehyde, hydroxycitronellal and cinnamic alcohol), 
and colophony. 

Patch testing to 26 fragrances was performed as a multi¬ 
center project in the European Union to further identify pos¬ 
sible additional allergens and prevent adverse reactions by 
proper labeling of cosmetic products [14]. The compounds 
considered important allergens were defined as group I 
substances: tree moss, HMPCC (hydroxymethylpentylcy- 
clohexene carboxaldehyde), oak moss, hydroxycitronellal, 
isoeugenol, cinnamic aldehyde, and farnesol. Group II 
included substances clearly allergenic, but less relevant 
regarding sensitization frequency: cinnamic alcohol, citral, 
citronellol, geraniol, eugenol, coumarin, lilial, amyl-cinnamic 
alcohol, and benzyl cinnamate. Rarely, substances in group 
III were sensitizers: benzyl alcohol, linalool, methylheptin 
carbonate, alfa-amyl-cinnamic aldehyde, alfa-hexyl- 
cinnamic aldehyde, limonene, benzyl salicylate, gamma- 
methylionon, benzyl benzoate, and anisyl alcohol [14]. 

Allergic reactions to Myroxylon pereira (balsam of Peru) 
have been correlated to scattered generalized dermatitis. 
Widespread involvement might also suggest a systemic 
exposure, and oral ingestion of balsam of Peru has been 
correlated with hand eczema [15]. 

Preservatives 

Preservatives are low molecular weight, biologically active 
compounds that prevent product contamination by micro¬ 


organisms, or degradation. The recent growing replacement 
of organic solvents and mineral oils to water-based products 
in the cosmetic industry has increased the need of preserva¬ 
tives. Distribution of the allergic rash includes face, neck, 
hands, axillae, or generalized. Common sensitizers include 
formaldehyde and formaldehyde releasers, thiomerosal, 
Kathon CG, parabens, glutaraldehyde, DMD-hydantoin, 
quaternium-15 and are widely present in water-containing 
products (e.g. shampoos, cosmetics, metalworking fluids, 
and soaps). 

Formaldehyde allergy is common and is mostly caused by 
formaldehyde-releasing biocides in cosmetics, toiletries, and 
other products. In a recent review of 81 formaldehyde- 
allergic patients, allergic reaction to at least one of the 12 
formaldehyde-releasing substances were detected in 79% of 
the cases and isolated reactions to releasers were rare [16]. 
Formaldehyde allergy is also reported as a common cause of 
occupational contact dermatitis and the professions at risk 
include hairdressers, healthcare workers, painters, photog¬ 
raphers, housekeeping personnel, metalworkers, masseurs, 
and workers dealing with creams, liquid soaps, and deter¬ 
gents [16]. 

Cleansing agents 

These are applied to remove sebum, desquamated cells, 
sweat, and microorganisms. Washout products are briefly in 
contact with the skin, therefore few cases of allergy have 
been reported. Allergens include surfactants (cocamidopro- 
pyl betaine), preservatives (methylchloroisothiozolinone), 
antimiocrobials (PCMX), and fragrances. 

Moisturizers 

Moisturizers inhibit transepidermal water loss by occlusion, 
and are composed of a mixture of substances such as petro¬ 
latum, lanolin, lanolin derivates, and fatty alcohols. Stasis 
dermatitis can be a predisposing factor for allergic contact 
dermatitis to lanolin. Self-tanning agents have become 
increasingly popular and are sold separately or in conjunc¬ 
tion with moisturizers. Such agents may cause allergic 
contact reactions when dihydroxyacetone degrades to form 
formaldehyde, formic acid, and acetic acid. 

Hydroquinone 

Hydroquinone is a whitening agent present in up to 2 % in 
over-the-counter creams and 4% in prescription bleaching 
creams. Irritant and allergic reactions, hypopigmentation 
and hyperpigmentation, and exogenous ochronosis are 
known side effects [17]. 

Shampoos and conditioners 

Shampoos contain a combination of cleansing agents and 
surfactants that act to remove sebum, scales, and microor¬ 
ganisms from the hair and scalp. Conditioner agents neutral¬ 
ize static charge and soften the hair. Common ingredients 


58 


7. Contact dermatitis and topical agents 


are moisturizers, oils, surfactants, lubricants, preservatives, 
and fragrances. Allergic reactions are uncommon because of 
the limited amount of time the substance is in contact with 
the skin, however, cocamidopropyl betaine (surfactant), for¬ 
maldehyde, methylchloroisothiazolone and methylisothia- 
zolone (preservatives) have been reported as causative 
agents of allergic contact dermatitis. 

Hair dyes and bleaches 

Hair dyes are classified in semi-permanent and permanent. 
Semi-permanent dyes are derivates from nitroanilines, 
nitrophenylenediamines, and nitroaminophenols which use 
low molecular weight elements that penetrate the hair 
cuticle. Permanent dyes act by the means of primary inter¬ 
mediates (/7-phenylenediamine [PPD] or ^-aminophenol) 
which are oxidized by hydrogen peroxide and react with 
different couplers to produce a wide range of colours. Once 
oxidized to para-benzo-quinone diamine, PPD is no longer 
allergenic [18]. A few exceptions include circumstances in 
which unreacted PPD remains in the skin, for instance with 
inadequate mixture of ingredients with the use of home¬ 
made coloring kits or poor rinsing. Distribution is on the 
hairline, scalp, face, and photo distributed. Consort derma¬ 
titis is defined as the presence of the allergic eruption in the 
partner of the subject using the allergenic substance. It has 
been described for cosmetics, including PPD [18]. 

Temporary henna tattooing and hair dying are common 
practices. Henna is a natural product derived from the leaves 
of Lawsonia inermis and rarely causes hypersensitivity reac¬ 
tion. The addition of PPD to henna causes contact sensitiza¬ 
tion to black henna and reported reactions include mild 
eczema to bullous reactions with scarring and pigmentation 
alterations [19]. 

Hair bleaches include hydrogen peroxide solutions that 
oxidize melanin and ammonium persulfate, a very strong 
oxidizing agent and a radical initiator, which can be used as 
a booster supplement in hair dyes. Type I and IV hypersen¬ 
sitivity reactions may arise from the use of ammonium 
persulfate. 

Permanents 

Permanents use mercaptans to cleave disufide bonds in hair; 
neutralizers are then added to reshape the configuration. 
Neutralizers contain hydrogen peroxide, bromates, per- 
bromates, percarbromates, or sodium borate perhydrate. 
Ammonium thioglycolate, also known as perm salt, is a 
cleaving agent and if applied improperly can cause extensive 
hair damage and acute contact irritant dermatitis. Glycerol 
monothioglycolate (GMTG, "acid" permanents) can cause 
allergic contact dermatitis. Storrs [20] demonstrated positive 
allergic reactions to GMTG in concentrations as low as 
0.25%, even when it was tested through glove fabric; 
however, household-weight neoprene gloves were proven 
to be protective. 


Nail products 

Nail polish and hardener contains nitrocellulose, resins, 
plasticizers, solvents and diluents, colors, and suspending 
agents. Most adverse reactions are secondary to tolysamide 
formaldehyde resin (toluene sulfonamide/formaldehyde 
resin). The dermatitis tends to affect places commonly 
reached by the fingers (e.g. face, eyelids, sides of the neck, 
mouth), sparing the hands and fingers. Nail elongation 
materials contain acrylics (ethy acrylate, 2-hydroxy ethyl 
acrylate, ethylene glycol dimethacrylate, ethyl cyanoacr¬ 
ylate, and triethylene glycol diacrylate) all previously 
reported as allergens. 

Local anesthetics 

Anesthetic agents can be divided in two groups: esters (ben- 
zocaine, tetracaine, and procaine) and amide derivates (lido- 
caine, mepivacaine, bupivacaine, etidocaine, andprilocaine). 
Cases of eczematous dermatitis have been reported second¬ 
ary to the use of topical ester agents and rarely secondary 
to amide derivates. Contact sensitization to 2.5% lidocaine 
and 2.5% prilocaine emulsion (EMLA, Astra Zeneca 
Pharmaceuticals LP, Wilmington, DE, USA) is rare, and 
additional uncommon side effects reported include purpuric 
eruption, rash, redness, itching, and edema [2]. 

True IgE-mediated reactions to injectable anesthetics 
correspond to less than 1 % of all adverse events. Although 
rare, such reactions may present as life-threatening events 
and prompt recognition of the symptoms and adequate 
management is imperative. In contrast, delayed-type 
reactions manifest within 12-48 hours and present as 
acute dermatitis (erythema, papules, vesicles and itching) 
[ 2 , 21 ]. 

The most common systemic adverse reactions to injectable 
anesthetics are psychosomatic responses, or exaggerated 
responses to epinephrine present in many products, caused 
by anxiety and vasovagal reflex. Patients may present with 
dyspnea, hyperventilation, and sympathetic responses, such 
as tachypnea, tachycardia, hypertension, and diaphoresis. 
Vasovagal syncope and peripheral paresthesias may also 
occur. Systemic toxicity occurs when excessive dosage is 
administered and manifest as light-headedness, tremors, 
restlessness, seizures, and depressed myocardial contra¬ 
ctility. Methemoglobulinemia is an idiosyncratic reaction 
reported with local injectable anesthetics [21]. 

Topical corticosteroids 

Non-halogenated topical steroids (hydrocortisone, budeso- 
nide) are the most common corticosteroids correlated with 
allergic reactions. Patients at risk are those with stasis der¬ 
matitis and chronic leg ulcers, followed by those with hand 
eczema, atopic dermatitis, anogenital, foot, and facial der¬ 
matitis. Patch testing with tixocortol pivalate and budeso- 
nide is useful to identify allergy to hydrocortisone and other 
steroids molecules that may cross-react [22]. 


59 


BASIC CONCEPTS Skin Physiology 


Injectables 

Botulinum toxin is a highly potent neurotoxin that inhibits 
acetylcholine release at the neuromuscular junction, block¬ 
ing neuromuscular transmission and reversibly paralyzing 
striated muscle. Allergic reactions are rare and include gen¬ 
eralized pruritus, psoriasiform eruption, urticaria, and ery¬ 
thema multiforme-type reactions [2,23]. 

Fillers can be classified as homogenous (polymer gels) and 
combination gels, which differ not only in composition, but 
also in duration of effect, tissue interaction properties, and 
type of adverse reactions evoked. Homogenous gels are the 
most commonly used and are subdivided into degradable 
(hyaluronic acid and collagen) and non-degradable gels 
(polyacrylamide and silicone). Degradable polymer gels 
resemble the elements commonly found in the tissues, 
therefore are degraded by naturally occurring enzymes, 
located in the extracellular matrix and/or within macro¬ 
phages [8]. Hence, fibrous response generated by these 
hydrophilic gels is minimal. Although generally considered 
safe, affordable, and ease to use, degradable gels are not 
permanent, and rare complications include allergic reac¬ 
tions, transient swelling, and cystic swelling [2,7]. 

Collagen fillers are substances derived from bovine col¬ 
lagen, which become non-allergenic after enzymatic diges¬ 
tion with pepsin. Formulations available on the market are 
collagen I (Zyderm I and II, INAMED Corporation, Santa 
Barbara, CA, USA) or cross-linked collagen (Zyplast, 
INAMED Corporation, Santa Barbara, CA, USA). Transient 
swelling and erythema are the most common reactions and 
tend to resolve a few days after the procedure. Hypersensitivity 
allergic reactions involve localized humoral and cellular 
inflammatory processes. Such reactions can persist up to 1 
year after the procedure and are strongly correlated with the 
presence of antibovine collagen antibodies, hence prophy¬ 
lactic testing of individuals is recommended. 

Silicone is the term applied to describe the medical group 
of compounds derived from silicone-containing synthetics. 
Polydimethylsiloxanes are the most commonly substances 
used and contain silicon, oxygen, and methane [9]. The 
silicon gel is hydrophobic and once introduced in the tissues 
it is dispersed in vacuoles or droplets, which may be absorbed 
by macrophages and foreign body giant cells. The cells may 
then migrate to the reticuloendothelial system and/or evoke 
a local foreign body reaction in the surrounding tissue. 
Phagocytes enter and transverse the gel, followed by gradual 
replacement with connective tissue [8]. 

Adverse reactions to soft tissue augmentation include 
bacterial infections, abscesses, local inflammation, discolora¬ 
tion, ulceration, migration, and formation of silicon-type 
granulomas [2,8]. Deep-seated panniculitis can present early 
as a tingling sensation followed by local edema [8]. Late 
signs include the presence of a solid, painless tumefaction, 
with or without facial disfigurement and facial nerve 
paralysis [10]. 


Occupational hand eczema 

Occupational hand eczema among hairdressers is a signifi¬ 
cant health problem and common sensitizers include hair 
dyes, ammonium persulfate, preservatives, amphoteric sur¬ 
factants, fragrances, and glycerol thioglycolate. The use of 
gloves, mild soaps, and moisturizing creams alleviate the 
condition but severe refractory cases may require definitive 
interruption of the occupational activity. Gloves worn as 
protection may also constitute a source of allergens for hand 
dermatitis in hairdressers and healthcare professionals. 


Diagnosis 

Diagnostic evaluation of patients with hypersensitivity reac¬ 
tions should be directed towards identifying the causative 
agent. Prick tests and radio allergo-sorbent tests (RASTs) are 
available for detection of IgE antibodies against specific aller¬ 
gens, therefore indicated for patients with some type I 
hypersensitivity reactions. 

Allergy to bovine collagen can be detected by intradermal 
challenge. The screening test is recommended for all cases 
prior to the procedure and consists of an intradermal injec¬ 
tion of 0.1 mL of the filler substance in the volar forearm, 
with evaluation of the reaction within 48-72 hours. A posi¬ 
tive test is defined as induration, erythema, tenderness, or 
swelling that persists or occurs longer than 6 hours after the 
injection. Positive subjects must be excluded from the pro¬ 
cedure. A second test is recommended for non-reactive sub¬ 
jects to lower the chances of treatment-associated adverse 
reactions. The test should be performed within 2 weeks after 
the initial exam, in the contralateral forearm or periphery 
of the face [2]. 

Patch-testing is required to diagnose delayed type IV aller¬ 
gic reactions. Epicutaneous application of standardized con¬ 
centrations of allergen chemicals on flat metal chambers are 
followed by occlusion and removal in 48 hours. The skin 
reaction is then graded and a second reading is performed 
in 1-3 days. The presence of induration, erythema, and/or 
vesicles denotes a positive reaction. 


Treatment 

Treatment is based on identifying the offending agent and 
lifetime avoidance. Type I reactions required blockage of 
histamine receptors. Severe anaphylactic reactions require 
immediate hospitalization for assessment of cardiorespira¬ 
tory status and intravenous fluids, subcutaneous epine¬ 
phrine, systemic steroids, and antihistaminic medication. 

Mild forms of contact allergic dermatitis are readily treat¬ 
able with avoidance of the offending agent. Topical steroids 
can be prescribed for a short period of time to hasten the 
process, whereas serious reactions may require addition of 
systemic immunosuppressant medication. 


60 




7. Contact dermatitis and topical agents 


Conclusions 

Cosmetic products are widely used and reactions to those 
products are commonly seen in daily dermatologic practice. 
Prompt recognition with identification and withdraw of the 
offending agent are key elements for successful manage¬ 
ment of such reactions. 

References 

1 Berne B, Tammela M, Farm G, Inerot A, Lindberg M. (2008) 
Can the reporting of adverse skin reactions to cosmetics be 
improved? A prospective clinical study using a structured pro¬ 
tocol. Contact Dermatitis 58, 223-7. 

2 Cohen DE, Kaufmann JM. (2003) Hypersensitivity reactions to 
products and devices in plastic surgery. Facial Plast Surg Clin 
North Am 11, 253-65. 

3 US Food and Drug Administration. (2005) FDA authority over 
cosmetics. CFSAN/Office of Cosmetics and Colors; 2005 [updated 
March 3, 2005; cited September 6, 2008]. Available from: http:// 
www.cfsan.fda.gov/~dms/cos-206.html 

4 Engasser PG, Maibach HI. (2003) Cosmetics and skin care in 
dermatologic practice. In: Freedberg IM, Eisen AZ, Wolff K, 
Austen KF, Goldsmith LA, Katz SI. Fitzpatrick's Dermatology in 
General Medicine , 6th edn. New York: McGraw-Hill, pp. 
2369-79. 

5 Cosmetic, Toiletry and Fragrance Association (CTFA). (2008) 
International Cosmetic Ingredient Dictionary and Handbook , 12th 
edn. Washington, DC: CTFA. 

6 Anderson JM, Rodriguez A, Chang DT. (2008) Foreign body 
reaction to biomaterials. Semin Immunol 20, 86-100. 

7 Cohen JL. (2008) Understanding, avoiding, and managing 
dermal filler complications. Dermatol Surg 34, S92-9. 

8 Christensen L. (2007) Normal and pathologic tissue reactions to 
soft tissue gel fillers. Dermatol Surg 33, SI68-75. 

9 Chasan PE. (2007) The history of injectable silicon fluids for 
soft-tissue augmentation. Plast Reconstr Surg 120, 2034-40. 

10 Poveda R, Bagan JV, Murillo J, Jimenez Y. (2006) Granulomatous 
facial reaction to injected cosmetic fillers: a presentation of five 
cases. Med Oral Patol Oral Cir Bucal 11, El-5. 


11 Jungbauer FH, Lensen GJ, Groothoff JW, Coenraads PJ. (2004). 
Exposure of the hands to wet work in nurses. Contact Dermatitis 
50, 225-9. 

12 Lammintausta K, Maibach HI, Wilson D. (1988) Mechanisms of 
subjective (sensory) irritation: propensity to non-immunologic 
contact urticaria and objective irritation in stingers. Derm Beruf 
Umwelt 36, 45-9. 

13 Primavera G, Berardesca E. (2005) Sensitive skin: mechanisms 
and diagnosis. Int J Cosmet Sci 27, 1-10. 

14 Schnuch A, Uter W, Geier J, Lessmann H, Frosch PJ. (2007) 
Sensitization to 26 fragrances to be labelled according to current 
European regulation: results of the IVDK and review of the 
literature. Contact Dermatitis 57, 1-10. 

15 Zug KA, Rietschel RL, Warshaw EM, Belsito DV, Taylor JS, 
Maibach HI, etal. (2008) The value of patch testing patients with 
a scattered generalized distribution of dermatitis: retrospective 
cross-sectional analyses of North American Contact Dermatitis 
Group data, 2001 to 2004. J Am Acad Dermatol 59, 426-31. 

16 Aalto-Korte K, Kuuliala O, Suuronen K, Alanko K. (2008) 
Occupational contact allergy to formaldehyde and formaldehyde 
releasers. Contact Dermatitis 59, 280-9. 

17 Draelos ZD. (2007) Skin lightening preparations and the hydro- 
quinone controversy. Dermatol Ther 20, 308-13. 

18 Veysey EC, Burge S, Cooper S. (2007) Consort contact derma¬ 
titis to paraphenylenediamine, with an unusual clinical presen¬ 
tation of tumid plaques. Contact Dermatitis 56, 366-7. 

19 Evans CC, Fleming JD. (2008) Images in clinical medicine: 
allergic contact dermatitis from a henna tattoo. N Engl J Med 
7, 627. 

20 Storrs FJ. (1984) Permanent wave contact dermatitis: contact 
allergy to glyceryl monothioglycolate. J Am Acad Dermatol 11, 
74-85. 

21 Phillips JF, Yates AB, Deshazo RD. (2007) Approach to patients 
with suspected hypersensitivity to local anesthetics. Am J Med Sci 
334, 190-6. 

22 English JS. (2000) Corticosteroid-induced contact dermatitis: a 
pragmatic approach. Clin Exp Dermatol 25, 261-4. 

23 Brueggemann N, Doegnitz L, Harms L, Moser A, Hagenah JM. 
(1008) Skin reactions after intramuscular injection of Botulinum 
toxin A: a rare side effect. J Neurol Neurosurg Psychiatry 79, 
231-2. 


61 



Part 2: Delivery of Cosmetic Skin Actives 


Chapter 8: Percutaneous delivery of cosmetic actives to 
the skin 

Marc Cornell, Sreekumar Pillai, and Christian Oresajo 

L'Oreal Research, Clark, NJ, USA 


BASIC CONCEPTS 

• Percutaneous delivery is the penetration of substances into the skin. 

• The goal of effective percutaneous delivery is to provide an effective amount of an active to the skin target site and thereby 
optimize efficacy while minimizing side effects. 

• The main barrier of the active permeation through the skin is the stratum corneum. The active must cross this skin barrier and 
permeate transepidermally to be delivered to the target site. 

• Molecules with a molecular weight of less than 500 Daltons penetrate the skin better than molecules with a larger molecular 
weight. The net charge of a molecule is important in enhancing penetration. 


Introduction 

Recent developments in new technologies combined with 
new knowledge in skin biology have advanced innovations 
in skin availability of actives and novel methods of sub¬ 
stance delivery. The goal of this chapter is to review new 
advances in delivery of actives to the skin and the effects 
of penetration enhancers. An understanding of the struc¬ 
ture of the skin is very important in managing active 
delivery. 


The basics 

The goal of percutaneous delivery is to provide an effective 
amount of an active to the skin target site and thereby opti¬ 
mize efficacy while minimizing side effects. This can be 
achieved by an understanding of the skin's complex struc¬ 
ture and by relying on physical and chemical parameters of 
vehicles applied to the skin. 

Skin physiology 

There are defined compartments and biologic structures 
within the skin that provide opportunities to deliver actives 
(Figure 8.1). Within these compartments there are many 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


chemical and biologic processes at work that may alter a 
given active or the physiology of skin target. 

The main barrier of active permeation through the skin is 
the stratum corneum. The active must cross this skin barrier 
and permeate transepidermally to be delivered to the target 
site, and the penetration can be moderated by the secretion 
activity of the appendages. This structure is located at the 
outermost layer of the epidermis [1]. This transepidermal 
route can be further subdivided into transcellular and inter¬ 
cellular routes [2]. Delivery of hydrophilic substances can be 
achieved through sweat gland route; however, this is also 
minimal in total volume. Therefore, the principal pathway 
for skin penetration of actives is the transepidermal route 
(route 1 in Figure 8.1). 

Active composition 

One of the first steps in understanding the phenomenon of 
active delivery is to completely characterize the active that 
is intended for delivery to the skin. There are well-known 
physical and chemical parameters that are specific to all 
chemical compounds. The essentials for characterization 
of actives are typically described in the literature or can 
be measured in the laboratory. This includes the active's 
molecular weight, dissociation constant (pK), solubility, and 
octanol/water [O/W] partition coefficient (log P). These 
parameters, along with a thorough understanding of the net 
ionic charge (cationic, anionic, and amphoteric) of the active 
will help in understanding its penetration profile. 

As general rule, molecules with a molecular weight of less 
than 500 Da penetrate the skin better than molecules with 


62 









8. Percutaneous delivery 



Figure 8.1 Possible pathways for a penetrant to cross the skin barrier. 
(1) across the intact horny layer; (2) through the hair follicles with the 
associated sebaceous glands; or (3) via the sweat glands. (This figure was 
published in: Daniels R. Strategies for skin penetration enhancement. 

Skin Care Forum 37, www.scf-online.com.) 


a larger molecular weight. It is also known that the net 
charge of a molecule is important in enhancing penetration. 
An un-ionized molecule penetrates the skin better than an 
ionized molecule. A thorough understanding of the relation¬ 
ship between the dissociation constant and formulation pH 
is critical. In many cases it is advantageous to keep the pH 
of a formulation near the pK of the active molecule in an 
attempt to enhance penetration. When looking at the parti¬ 
tion coefficient, molecules showing intermediate partition 
coefficients (log P 0/W of 1-3) have adequate solubility 
within the lipid domains of the stratum corneum to permit 
diffusion through this domain while still having sufficient 
hydrophilic nature to allow partitioning into the viable 
tissues of the epidermis [3]. 

Fick's law 

The permeation of active across the stratum corneum is a 
passive process, which can be approximated by Fick's first 
law: 


J = —j—(C) (equation 8.1) 

This defines steady-state flux (J) is related to the diffusion 
coefficient (D) of the active in the stratum corneum over a 
diffusional path length or membrane thickness (L), the par¬ 
tition coefficient (K) between the stratum corneum and the 
vehicle, and the applied drug concentration (C) which is 
assumed to be constant. 

Novel formulation strategies allow for manipulation of 
the partition coefficient (K) and concentration (C). Skin 
penetration can be enhanced by the following strategies: 


1 Increasing drug diffusion in the skin; 

2 Increasing drug solubility in the skin; and/or 

3 Increasing the degree of saturation of the drug in the 
formulation [4]. 

Equation (1) aids in identifying the ideal parameters 
for the diffusion of the active across the skin. The influence 
of solubility and partition coefficient on diffusion across 
the stratum corneum has been extensively studied in the 
literature [3]. 


Vehicle effect 

Delivery of actives from emulsions 

The key for evaluation of the vehicle effect is to understand 
the dynamics between the vehicle and the active. Based on 
the physical and chemical nature of the active there are 
specific formulation strategies that can be designed to 
enhance delivery of actives. 

The primary vector for topical delivery of actives is a semi¬ 
solid ointment or emulsion base. The main reason for selec¬ 
tion of this dosage form is convenience and cosmetic 
elegance. Emulsions are convenient because they typically 
have two phases (hydrophilic and hydrophobic). The bi- 
phasic nature allows for placement of actives based on solu¬ 
bility and stability. This allows the formulator to bring 
lipophilic and hydrophilic actives into the dosage form while 
maintaining the optimized stability profile. The effect of the 
type of vehicle has been well described in the literature [6]. 
Numerous references are available for altering the delivery 
of actives from various emulsion forms (0/W, W/0, multiple 
emulsions, and nano-emulsions). 


Formulation strategies 

A basic formulation has many components. Table 8.1 pro¬ 
vides an overview of these formula components and also 
provides a brief summary of the anticipated effect on active 
delivery. Some of these chemical functions are more clearly 
defined below in discussion on chemical penetration 
enhancers. 

The ability of vehicles to deliver actives is tied to an under¬ 
standing of diffusion of actives through various skin com¬ 
partments (epidermal and dermal). Diffusion of actives 
across the skin is a passive process. Compounds with low 
solubility and affinity for the hydrophilic and lipophilic com¬ 
ponents of the stratum corneum would theoretically parti¬ 
tion at a slow rate. These difficulties may be overcome by 
adding a chemical adjunct to the delivery system that would 
promote partitioning into the stratum corneum. Partitioning 
of actives from the dosage form is highly dependent on the 
relative solubility of the active in the components of the 
delivery system and in the stratum corneum. Thus, the for¬ 
mulation of the vehicle may markedly influence the degree 


63 























BASIC CONCEPTS Delivery of Cosmetic Skin Actives 


Table 8.1 Formulation components. 

Ingredient 

Chemical function 

Effect on delivery 

Water 

Carrier/solvent 

Hydration 

Alcohol 

Carrier/solvent 

Fluidizes stratum corneum, alters 
permeability of stratum cornuem 

Propylene glycol 

Co-solvent/humectant 

Alter permeability of stratum corneum 
Alter vehicle stratum corneum 
partition coefficient 

Surfactant 

Emulsifier/stabilizer 

Emulsion particle size reduction, 
active solubilizer 

Emollient 

Skin conditioner, 

active carrier 

Alter stratum corneum permeability 

Alter vehicle stratum corneum 
partition coefficient 

Delivery system 

Protect/target actives 

Targeted/enhanced active penetration 


of penetration of the active. Percutaneous absorption 
involves the following sequences: 

• Partitioning of the molecule into the stratum corneum 
from the applied vehicle phase; 

• Molecular diffusion through the stratum corneum; 

• Partitioning from the stratum corneum into the viable 
epidermis; and 

• Diffusion through the epidermis and upper dermis and 
capillary uptake [7]. 

One of the most effective formulation techniques to boost 
active penetration is supersaturation. This chemical process 
happens when an active's maximum concentration in solu¬ 
tion is exceeded by the use of solvents or co-solvents. This 
type of solution state can happen during the evaporation 
of an emulsion on the skin. As water evaporates from a 
cream rubbed on the skin a superconcentrate depot of 
active forms on the skin. This creates a diffusional concen¬ 
tration gradient across the stratum corneum. One can 
attempt to boost this effect even further in the formulation 
by slightly exceeding the maximum solubility of the active 
in the formula using co-solvents. Supersaturation is an 
effective technique but the disadvantage is that active 
recrystallization can take place in this highly concentrated 
solution state. There are crystallization inhibitors that can 
be added to supersaturated solution but many experimental 
data need to be collected on this type of formulation 
strategy. 

Eutectic blends are formulation techniques that can 
enhance penetration of actives. The melting point of an 
active influences solubility and hence skin penetration. 
According to solution theory, the lower the melting point, 
the greater the solubility of a material in a given solvent, 
including skin lipids. The melting point can be lowered by 


formation of a eutectic mixture. This mixture of two com¬ 
ponents which, at a certain ratio, inhibits the crystalline 
process of each other such that the melting point of the 
two components in the mixture is less than that of each 
component alone. In all cases, the melting point of the 
active is depressed to around or below skin temperature 
thereby enhancing solubility. This technique has been 
used to enhance the penetration of ibuprofen through the 
skin [8]. 

Manipulation of the vehicle skin partition coefficient of a 
formulation can be used as an overall formulation strategy 
to boost penetration of actives. This can be done by altering 
the solubility of the active in the vehicle via selection of 
different excipients. This change in the solubility parameter 
(5) of the excipients can be tuned so that the active is more 
soluble in the stratum corneum than in the vehicle. Hence 
the diffusional gradient is altered towards the skin and 
thereby enhancing penetration. It has been shown that a 
solvent capable of shifting the solubility parameter (8) of the 
skin closer to that of the activate will active flux rate [9]. 
Another strategy is to add a penetration enhancer that alters 
the membrane permeability of the skin. This strategy is dis¬ 
cussed in more detail below. 

Skin occlusion can increase stratum corneum hydration, 
and hence influence percutaneous absorption by altering 
partitioning between the surface chemical and the skin 
because of the increasing presence of water, swelling cor- 
neocytes, and possibly altering the intercellular lipid phase 
organization, also by increasing the skin surface tempera¬ 
ture, and increasing blood flow [10]. 

The ultimate goal of penetration enhancement is to target 
the active in the stratum corneum and/or epidermis without 
allowing for systemic absorption. This remains the biggest 


64 





8. Percutaneous delivery 


challenge for active penetration enhancement and it is one 
of the keys for targeted active delivery. 


Penetration enhancers 

In this section, the influence of penetration enhancers on 
the diffusion coefficient and solubility of the active in the 
stratum corneum is evaluated. The use of topically applied 
chemical agents (surfactants, solvents, emollients) is a well- 
known technique to modify the stratum corneum and also 
modify the chemical potential of selected actives. Collectively, 
these materials can be referred to as penetration enhancers 
(PEs). Based on the chemical structure, PEs can be catego¬ 
rized into several groups such as fatty acids, fatty alcohols, 
terpene fatty acid esters, and pyrrolidone derivatives [11]. 
PEs commonly used in skin care products have well-known 
safety profiles but their ability to enhance penetration of an 
active is challenging because of the manifold ingredients 
used in many formulations. 

Solvents 

A number of solvents (e.g. ethanol, propylene glycol, 
Transcutol® [Gattefosse, Saint-Priest, France] and A-methyl 
pyrrolidone) increase permeant partitioning into and solu¬ 
bility within the stratum corneum, hence increasing K P in 
Fick's equation (equation 1). Ethanol was the first penetra¬ 
tion enhancer co-solvent incorporated into transdermal 
systems [12]. Synergistic effects between enhancers (e.g. 
Azone® [PI Chemicals, Shanghai, China], fatty acids) and 
more polar co-solvents (e.g. ethanol, propylene glycol) have 
also been reported suggesting that the latter facilitates the 
solubilization of the former within the stratum corneum, 
thus amplifying the lipid-modulating effect. Similarly, sol¬ 
vents such as Transcutol are proposed to act by improving 
solubility within the membrane rather than by increasing 
diffusion. Another solvent, dimethylsulfoxide (DMSO), by 
contrast, is relatively aggressive and induces significant 
structural perturbations such as keratin denaturation and 
the solubilization of membrane components [13]. 

Physical enhancers 

In addition to the chemical penetration enhancers discussed 
above, there is another class of penetration enhancers 
known as physical penetration enhancers. These materials 
stand between chemical enhancers and penetration enhancer 
devices. This unique classification is because in most cases 
the materials are particles of chemical origin (polyethylene, 
salt, sugar, aluminum oxide) but require physical energy to 
exert an action on the skin. These materials are used to 
physically debride or excoriate the stratum corneum by 
abrasive action. This is typically done by rubbing the parti¬ 
cles by hand on the skin. New high-tech devices are now 


available that propel an abrasive against the skin thereby 
stripping away the stratum corneum. 


Penetration enhancement vectors 

There are customized carriers (vectors) for delivery of actives 
to the skin. These vectors are a type of vehicle that allow 
for enhanced penetration via their small size and unique 
physical chemical composition. These vectors are known as 
submicron delivery systems (SDS). Discussion focuses on 
liposomes, niosomes, lipid particles, and nanocapsules. 

Liposomes 

Liposomes are colloidal particles formed as concentric bio- 
molecular layers that are capable of encapsulating actives. 
The lipid bilayer structure of liposomes mimics the barrier 
properties of biomembranes, and therefore they offer the 
potential of examining the behavior of membranes of a 
known composition. Thus, by altering the lipid composition 
of the bilayer or the material incorporated, it is possible to 
establish differences in membrane properties. Liposomes 
store water-soluble substances inside like biologic cells. The 
phospholipids forming these liposomes enhance the pene¬ 
tration of the encapsulated active agents into the stratum 
corneum [14]. 

There is debate on liposome formulations and their mode 
of action regarding penetration enhancement. Variation in 
performance may be caused by the variation in formulation 
and method of manufacture used to prepare this delivery 
form. Several factors such as size, lamellarity (unilamellar 
vs. multilamellar), lipid composition, charge on the lipo¬ 
somal surface, mode of application, and total lipid concen¬ 
tration have been proven to influence deposition into the 
deeper skin layers. It is reported by several authors that the 
high elasticity of liposome vesicles could result in enhanced 
transport across the skin as compared to vesicles with rigid 
membranes. 

Liposomes have a heterogeneous lipid composition with 
several coexisting domains exhibiting different fluidity char¬ 
acteristics in the bi-layers. This property can be used to 
enhance the penetration of entrapped actives into the skin. 
It is supposed that once in contact with skin, some budding 
of liposomal membrane might occur. This could cause a 
mixing of the liposome bi-layer with intracellular lipids in 
the stratum corneum which may change the hydration con¬ 
ditions and thereby the structure of lipid lamellae. This may 
enhance the permeation of the lipophilic active into the 
stratum corneum and ease the diffusion of hydrophilic 
actives into the interlamellar spaces [13]. 

Niosomes 

Niosomes are formed by blending non-ionic surfactants of 
the alkyl or dialkyl polyglycerol ether class and cholesterol 


65 




BASIC CONCEPTS Delivery of Cosmetic Skin Actives 


with subsequent hydration in aqueous media. These vesicles 
can be prepared using a number of manufacturing processes: 
ether injection, membrane extrusion, microfluidization, and 
sonication. Niosomes have an infrastructure consisting of 
hydrophilic, amphiphilic, and lipophilic moieties together 
and as a result can accommodate active molecules with a 
wide range of solubilities. They can be expected to target the 
active to its desired site of action and/or to control its release 
[16]. Niosomes are similar to liposomes in that they both 
have a bi-layer structure and their final form depends on 
the method of manufacture. There are structural similarities 
between niosomes and liposomes but niosomes do not 
contain phospholipids. This provides niosomes with a better 
stability profile because of improved oxidative stability. 

Solid lipid nanoparticles 

Solid lipid nanoparticles (SLNP) were developed at the 
beginning of the 1990s as an alternative carrier system to 
emulsions, liposomes, and polymeric nanoparticles. SLNP 
have the advantage of requiring no solvents for production 
processing and of relatively low cost for the excipients. SLNP 
represents a particle system that can be produced with an 
established technique of high-pressure homogenization 
allowing production on an industrial scale. This method also 
protects the incorporated drug against chemical degradation 
as there is little or no access for water to enter the inner area 
core of the lipid particle [17]. Lipid particles can be used as 
penetration enhancers of encapsulated actives through the 
skin because of their excellent occlusive and hydrating prop¬ 
erties. SLNP have recently been investigated as carriers for 
enhanced skin delivery of sunscreens, vitamins A and E, 
triptolide, and glucocorticoids [18]. 

Nanocapsules 

Nanocapsules are a type of submicron delivery system (SDS). 
This technology can segregate and protect sensitive materials 
and also control the release of actives. The more obvious 
opportunity for penetration enhancement of actives is 
because of their small size (20-1000nm in diameter). 


Nanocapsules can be formed by preparing a lipophilic core 
surrounded by a thin wall of a polymeric material prepared 
by anionic polymerization of an alkylcyanoacrylate 
monomer. These very safe types of system have been pro¬ 
posed as vesicular colloidal polymeric drug carriers. 
Nanocapsules have the ability to enhance penetration but 
they can also control delivery of actives to the skin. 

In a recent study, indomethacin was nano-encapsulated 
for topical use. This study compared cumulative release of 
indomethacin dispersed in gel base with indomethacin 
nano-encapsulated and indomethacin nano-encapsulated in 
a gel. The highest delivery was achieved with the nanoen- 
capsulated indomethacin (Figure 8.2). 


Devices for penetration enhancement 

Devices for enhancing skin penetration of actives are at the 
leading edge of skincare technology. When utilizing devices 
for enhanced penetration of actives it is imperative to look 
into the regulatory classification of these instruments. The 
FDA has several guidelines and requirements for medical 
devices (510K). The 51 OK regulatory classification is impor¬ 
tant for safety and efficacy of any consumer device product 
and an understanding of the regulatory landscape in this 
area is essential. Four device technologies are reviewed. 
They range from moderately invasive to mildly invasive in 
terms of effect on the skin. In all cases, the goal is to revers¬ 
ibly alter the skin barrier function by physical or electroen- 
ergetic means. 

Ultrasound waves 

Ultrasound waves are sound waves that are above the 
audible limit (>20kH). During ultrasound treatment the skin 
is exposed to mechanical and thermal energy which can 
alter the skin barrier property. Thermal and non-thermal 
characteristics of high-frequency sound waves can enhance 
the diffusion of topically applied actives. Heating from ultra¬ 
sound increases the kinetic energy of the molecules in the 



Time (hours) 


Figure 8.2 Cumulative amount of indomethicin 
(initial loading 0.5% w/v) per unit area, permeating 
through excised rat skin when released from PNBCA 
nanocapsule dispersion in pH 7.4 phosphate buffer, 
PNBCA nanocapsule dispersion in Pluronic F-127 gel 
and 25% w/w Pluronic F-127 gel. Each value is the 
mean ± SE of four determinations. (This figure was 
published in: Miyazaki S, Takahashi A, Kubo W, 
Bachynsky J, Lobenberg R. (2003) Poly 
n-butylcyanoacrylate (PNBCA) nanocapsules as a carrier 
for NSAIDs: in vitro release and in vivo skin 
penetration. J Pharm Pharmaceut Sci 6, 238-45.) 


66 











8. Percutaneous delivery 


active and in the cell membrane. These physiologic changes 
enhance the opportunity for active molecules to diffuse 
through the stratum corneum to the capillary network in 
the papillary dermis. The mechanical characteristics of the 
sound wave also enhance active diffusion by oscillating the 
cells at high speed, changing the resting potential of the cell 
membrane and potentially disrupting the cell membrane of 
some of the cells in the area [19]. 

A recent study on the use of ultrasound and topical skin 
lightening agents showed the effect of high-frequency ultra¬ 
sound together with a gel containing skin-lightening agents 
(ascorbyl glucoside and niacinamide) on facial hyperpig¬ 
mentation in vivo in Japanese women [20]. 

Patches 

Delivery patches have been available for some time. One of 
the first applications of patch technology was in a transder- 
mal motion sickness (scopolamine) patch. There are com¬ 
mercial products that provide actives in a patch formula. 
They utilize adhesive technology or a rate-limiting porous 


membrane to target and localize the actives. Some common 
patch applications are directed towards reduction of age 
spots or dark circles under the eye. The key delivery enhance¬ 
ment for patches is a combination of localized delivery and 
occlusion. 

Microneedles 

Another type of delivery device is the microneedle. 
Microneedles are similar to traditional needles, but are 
fabricated at the micro size. They are generally 1 pm in 
diameter and range 1-100pm in length (Figure 8.3). The 
very first microneedle systems consisted of a reservoir and 
a range of projections (microneedles 30-100mm long) 
extending from the reservoir, which penetrated the stratum 
corneum and epidermis to deliver the active. The micronee¬ 
dle delivery system is not based on diffusion as in other 
transdermal drug delivery products but based on the tem¬ 
porary mechanical disruption of the skin and the placement 
of the active within the epidermis, where it can more readily 
reach its site of action. Microneedles have been fabricated 


Figure 8.3 Solid microneedles fabricated out of 
silicon, polymer, and metal, imaged by scanning 
electron microscopy, (a) Silicon microneedle (150pm 
tall) from a 400-needle array etched out of a silicon 
substrate, (b) Section of an array containing 160000 
silicon microneedles (25pm tall), (c) Metal microneedle 
(120pm tall) from a 400-needle array made by 
electrodepositing onto a polymeric mold, (d-f) 
Biodegradable polymer microneedles with beveled tips 
from 100-needle arrays made by filling polymeric 
molds, (d) Flat-bevel tip made of polylactic acid 
(400pm tall), (e) Curved-bevel tip made of polyglycolic 
acid (600pm tall), (f) Curved-bevel tip with a groove 
etched along the full length of the needle made of 
polyglycolic acid (400pm tall). (This figure was 
published in: McAllister DV, Wang PM, Davis SP, 

Park JH, Canatella PJ, Allen MG, eta/. (2003) 
Microfabricated needles for transdermal delivery of 
macromolecules and nanoparticles: fabrication methods 
and transport studies. Proc Natl Acad Sci USA 100, 
13755-13760.) 



67 



BASIC CONCEPTS Delivery of Cosmetic Skin Actives 


with various materials such as metals, silicon, silicon dioxide, 
polymers, glass, and other materials. There are already 
patents granted for these types of moderately invasive 
delivery system [21]. 

Iontophoresis 

Iontophoresis is a technology that has been brought to the 
cosmetic industry via the pharmaceutical development field. 
Iontophoresis passes a small direct current through an 
active-containing electrode placed in contact with the skin, 
with a grounding electrode to complete the circuit. Three 
important mechanisms enhance transport: 

1 The driving electrode repels oppositely charged species; 

2 The electric current increases skin permeability; and 

3 Electro-osmosis moves uncharged molecules and large 
polar peptides [22]. 

There are limitations related to this technique. The active 
ingredient must be water-soluble, ionic, and with a molecu¬ 
lar weight below 5000 Da. Even with all of these limitations, 
reported data show that the drug delivery effectiveness can 
be increased by one-third through iontophoresis [23]. 


In vitro and in vivo delivery assessment 

A key in any evaluation assessment of skin bioavailability of 
actives is a quantitative measurement of activity by in vitro 
and in vivo methods. In early development phases in vitro 
methods provide a quick, reproducible way to identify 
promising formulations for next phase development studies. 
There are different techniques for evaluating percutaneous 
absorption of actives. 

Franz cell 

A well-known technique for measuring in vitro skin per¬ 
meation is the Franz cell apparatus (Figure 8.4). The test 
apparatus and technique have been well documented for 
use within the pharmaceutical and cosmetic industries [24]. 
The technique utilizes a sampling cell which contains a 


solution reservoir and a sampling port, the top portion of 
the Franz cell is covered with a biologic membrane or skin 
substitute. The formulation is added to the top of the cell 
and periodic samples are taken from the cell reservoir and 
assays are plotted versus time to develop a time-penetration 
profile. 

Tape stripping 

Tape stripping is a technique used for in vivo active penetra¬ 
tion evaluation. In this procedure, penetration of the active 
is estimated from the amount recovered in the stratum 
corneum by adhesive tape stripping at a fixed time point 
following application [25]. This technique is also recognized 
by FDA as a viable screening option for dermatologic evalu¬ 
ation [26]. 

Microdialysis 

During the last decade, microdialysis has been shown to be 
a promising technique for the assessment of in vivo and ex 
vivo cutaneous delivery of actives. The technique is based on 
the passive diffusion of compounds down a concentration 
gradient across a semi-permeable membrane forming a thin 
hollow "tube" (typically, a few tenths of a millimeters in 
diameter), which - at least, in theory - functionally repre¬ 
sents a permeable blood vessel (Figure 8.5.). Two kinds of 
probe are in common use: linear and concentric. 

Confocal Raman microspectroscopy 

Confocal Raman microspectroscopy (CRS) is a new, non- 
invasive technique which can be used for in vivo skin 
penetration evaluation. This technique combines Raman 
spectroscopy with confocal microscopy. CRS is a non¬ 
destructive and rapid technique that allows information to 
be obtained from deep layers under the skin surface, giving 
the possibility of a real-time tracking of the drug in the skin 
layers. The specific Raman signature of the active agent 
enables its identification within the skin [27]. 

There is a range of techniques of in vitro and in vivo evalu¬ 
ation for following penetration of actives through the skin. 



Figure 8.4 The Franz diffusion chamber. 


68 


































8. Percutaneous delivery 


Figure 8.5 The microdialysis apparatus for the evaluation 
of penetration through the human skin barrier. (This figure 
was published in: Schnetz E, Fartasch M. (2001) 
Microdialysis for the evaluation of penetration through the 
human skin barrier: a promising tool for future research? 
EurJ Pharm Sci 12, 165-74.) 


Microdialysis 
pump 



Stratum corneum — 
Viable epidermis-1 

Dermis 


I Solutel 


Diffuson of solutes 
into the perfusate 


Dia lysate 


Table 8.2 Methods to assess drug penetration into and/or across the skin. (From Herkenne C, et al. (2008) In vivo methods for the assessment of 
topical drug bioavailability. Pharm Res 25, 87-103.) 



Method 

Measure 

Measurement site 

Temporal resolution 

Technical simplicity 

In vitro 

Diffusion cell 

Q 

Transport into and across skin 

++ 

+ 

In vivo: non- or 
minimally invasive 

Tape stripping 

Q 

Stratum corneum 

0 

+ 

ATR-FTIR 

Q 

Stratum corneum 

+ 

+ 


Raman 

Q/L 

Upper skin 

+ 

+ 


Microdialysis 

Q (free) 

Dermis (or subdermis) 

++ 

- 


Vasoconstriction 

A 

Microcirculation 

+ 

± 

In vivo: invasive 

Blister 

Q 

Extracellular fluid 

0 

± 


Biopsy 

Q 

Skin 

0 

+ 


Biopsy 

Q + L 

Skin (depth) 

0 

± 


Q, quantity of drug; A, pharmacological activity of drug; L, drug localization. 


Some are more invasive than others and some are more 
predictive across various dosage forms utilized on the skin. 
In Table 8.2 a summary chart shows a good comparison of 
the techniques based on strengths and weaknesses. 


Conclusions and future trends 

There are many formulation options available for delivering 
actives to targets within the skin. Understanding the skin 
and its interaction with various actives allows the chemist 
to select delivery options that provide safe and effective 
properties. 

A good understanding of the physicochemical parameters 
of the active and the desired skin target are needed before 
deciding on a particular delivery option. Human studies are 
the "gold standard" against which all methods for measuring 
percutaneous absorption should be judged. The conduct of 
human volunteer experiments is well regulated. Study pro¬ 
tocols and accompanying toxicologic data must be submitted 
to an ethics committee for approval [28]. 


Next generation delivery technologies are being devel¬ 
oped and in some cases are already on the way to the 
market. Researchers from device and skincare companies 
are already in collaboration to bring combinations of devices 
and actives to the field of cosmetic dermatology. The 
approach can vary from non-invasive LEDs all the way to 
more invasive, laser-based enhanced penetration of actives. 
There are many home-use devices coming to the market 
today. These advances in delivery technology will likely 
culminate in a commercially available topical product that 
has its efficacy boosted by some type of chemical or physical 
delivery device as demonstrated in the delivery of estradiol 
using either a delivery vesicle (ultra-deformable liposomes) 
or a device (iontophoresis) [29]. 

References 

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York: Marcel Dekker Inc., p. 303. 

2 Barry BW. (1987) Penetration enhancers in pharmacology and 
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Basel: Karger; Vol. 1, pp. 121-37. 


69 





























BASIC CONCEPTS Delivery of Cosmetic Skin Actives 


3 Heather A, Benson E. (2005) Current drug delivery, penetration 
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4 Moser K, Kriwet K, Naik A, Kalia YN, Guy RH. (2001) Passive 
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8 Stott PW, Williams AC, Barry BW. (1998) Transdermal delivery 
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17 Kreuter J. (1994) Nanoparticles. In: Kreuter J, ed. Colloidal Drug 
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19 Dinno MA, Crum LA, Wu J. (1989) The effect of therapeutic 
ultrasound on the electrophysiologic parameters of frog skin. 
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6565532. Micro needle apparatus semi-permanent subcutane¬ 
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22 Barry BW. (2001) Is transdermal drug delivery research still 
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23 Yao N, Gnaegy M, Haas C. (2004) Iontophoresis transdermal 
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25 Rougier A, Dupuis D, Lotte C. (1989) Stripping method for 
measuring percutaneous absorption in vivo. In: Bronaugh RL, 
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26 Shah VP, Flynn GL, Yacobi A, Maibach HI, Bon C, Fleischer NM, 
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167-71. 

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Int J Pharm 240, 55-66. 


70 


Chapter 9: Creams, lotions, and ointments 

Irwin Palefsky 

Cosmetech Laboratories Inc., Fairfield, NJ, USA 


BASIC CONCEPTS 

• Creams, lotions, and ointments are both vehicles and delivery systems for dermatologic products. 

• Creams and lotions are emulsions, which are colloidal dispersions comprising two immiscible liquids (e.g. oil and water), one of 
which is dispersed as droplets representing the internal or discontinuous phase within the other external phase. 

• Ointments are semi-solid preparations used topically for protective emollient effects or as vehicles for the local administration of 
medicaments. 

• Ointments are mixtures of fats, waxes, animal and plant oils, and solid and liquid hydrocarbons. 


Introduction 

This chapter examines creams, lotions, and ointments as 
both vehicles and delivery systems for dermatologic prod¬ 
ucts. Creams, lotions, and ointments have a unique compo¬ 
sition that can alter the ability of ingredients to reach the 
skin surface while also influencing product esthetics. The 
construction of the cream or ointment is an important deter¬ 
mining factor in patient compliance, because if patients do 
not like the feel, smell, or color of a dermatologic they will 
not properly follow directions for its use. 


Definition of creams, lotions, 
and ointments 

Creams and lotions 

Creams and lotions are classified as emulsions. There are 
several different types of emulsions that function as a vehicle 
and delivery system for cosmetic and drug materials. The 
classic definition of an emulsion is a colloidal dispersion 
comprising two immiscible liquids (e.g. oil and water), one 
of which is dispersed as droplets representing the internal or 
discontinuous phase within the other external phase [1]. All 
emulsions require the inclusion of an emulsifier or dispers¬ 
ing agent responsible for keeping the two immiscible phases 
together for an extended period of time. All emulsions are 
unstable and will eventually separate into two or more 
phases. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Emulsions can be classified as a cream or lotion. There are 
no legal definition differences between a cream and a lotion. 
The determination of what constitutes a cream or lotion 
emulsion is determined by viscosity. If an emulsion can be 
poured from a bottle or pumped from a jar, it is labeled a 
lotion. If the emulsion requires a jar or a tube for dispensing 
and does not readily flow, it is labeled a cream. The term 
emulsion will be used for the remainder of this chapter to 
indicate a cream or lotion. 

The other important part of the definition of an emulsion 
is based on the materials that comprise the internal phase 
and the materials that comprise the external or continuous 
phase. The two categories of emulsions are oil-in-water 
(O/W) and water-in-oil (W/O). The names describe the 
composition of the emulsion (Figure 9.1). 

Emulsions can also be described by their emulsifier type 
as anionic, cationic, and non-ionic. This terminology refers 
to the ionic charge, or lack of charge, on the emulsifier 
system. Emulsions have also been developed that are based 
on polymeric emulsifiers and liquid crystal emulsifiers. 
These emulsions are different from traditional emulsions, 
because the two phases are held together by different mech¬ 
anisms. Sophisticated emulsion technology is beyond the 
scope of this chapter; however, additional information can 
be found in Bloch [1]. 

Ointments 

Ointments can be defined as semi-solid preparations used 
topically for protective emollient effects or as vehicles for the 
local administration of medicaments. They are mixtures of 
fats, waxes, animal and plant oils, and solid and liquid 
hydrocarbons [2]. Ointments are traditionally anhydrous 
bases, meaning they do not contain water, and therefore 
pose fewer microbial contamination issues than emulsions, 
which is a distinct advantage. In addition, because ointments 


71 







BASIC CONCEPTS Delivery of Cosmetic Skin Actives 




Oil in water 


Figure 9.1 Different emulsion types. (This figure is from "Emulsions" 
presentation from Cognis Corp. August 2004.) 


Table 9.1 Generic composition of a typical oil-in-water emulsion. 

Ingredients 

% (weight/weight) 

Water phase 


Deionized water 

60.0-90.0 

Humectant 

2.00-7.0 

Preservative* 

0.05-0.5 

Water-soluble 

emulsified 

0.25-2.5 

Thickener(s) 

0.1-1.0 

Water-soluble emollient 

0.5-2.0 

Chelating agent 

0.05-0.20 

Oil phase 


Emollient system - oils, 
esters, silicones, etc. 

3.0-15.0 

Oil-soluble emulsifiers 

2.0-5.0 

"Active ingredients" 

As required by regulations 

Oil-soluble antioxidants 

0.05-0.5 

Fragrance/essential oil, 

etc. 

0.1-2.0 

Color 

As required 

Preservative * 

0.05-1.0 

pH adjustments 

As required 

* Preservatives are frequently added in two places in the formulation. 

+ May also be added into the oil phase. 


are anhydrous in nature, they tend to be more water- 
resistant than emulsions. However, ointments have less 
esthetic appeal for skin care and dermatology products as 
they are frequently described as oily, waxy, greasy, sticky, 
tacky, and heavy. Ointments are used more commonly for 
the delivery of medications than for skin care products 
because of their undesirable esthetics. 


Table 9.2 Atypical "non-ionic" oil-in-water emulsion base. 


Ingredients 

Function 

% 

weight/weight 

Water phase 



Deionized water 

External phase vehicle 

82.95 

Carbomer 

Thickener 

0.20 

Disodium EDTA 

Chelating agent 

0.10 

Butylene glycol 

Humectant 

2.00 

Oil phase 



Cetearyl alcohol (and) 
ceteaeth-20 

Emulsifier 

2.00 

Cyclopentasiloxane 

Silicone emollient 

4.00 

Dimethicone 

Silicone emollient 

1.00 

Caprylic/capric 

triglyceride 

Organic emollient 

5.00 

Glyceryl stearate (and) 
PEG 100 stearate 

Emulsifier 

1.25 

Triethanolamine (99%) 

Neutralizing agent 
and pH adjuster 

0.50 

Preservative 

Antimicrobial 

1.00 


The pH of this cream would be 5.5-6.5. 

The viscosity would be approximately 15 000-25000 centipoise. 


Composition of creams and ointment 

Oil-in-water creams 

The most popular type of emulsion used in skin care prod¬ 
ucts and cosmeceuticals is oil-in-water (O/W). A generic 
composition for an O/W emulsion is presented in Table 9.1 
[3]. Each of the ingredient classes are discussed in detail to 
aid in the understanding of O/W formulations. A typical 
"non-ionic" oil-in-water emulsion composition is shown in 
Table 9.2. 

Emulsifiers 

Emulsifiers are important to keep the oil and water ingredi¬ 
ents miscible. The choice of emulsifier will also determine 
the emulsion pH and effect the application and stability of 
the emulsion, as well as the delivery of materials into the 
skin. Emulsifiers can damage the skin barrier by emulsifying 
the sebum and intercellular lipids. This has led to the need 
to develop "skin friendly emulsifiers." These emulsifiers do 
not adversely affect the barrier properties of the skin and in 
some cases even help maintain barrier properties. Because 
the route of delivery into the skin is primarily through the 
lipid layer, which constitutes the mortar in the "brick and 


72 










9. Creams, lotions, and ointments 


mortar" model of the skin, the selection of an emulsifier can 
determine whether the disruption of the lipid layer. 

Liquid crystal forming emulsifiers are being used more 
frequently because they maintain the skin barrier. These 
emulsifiers function like the phospholipids and ceramides 
found in the skin and therefore do not disrupt barrier func¬ 
tion because of their skin lipid compatibility. A popular 
liquid crystal forming emulsifier is lecithin or hydrogenated 
lecithin [4]. 

Another recent trend is the use of emulsifiers as part of 
the emollient system in the product. Emollients are sub¬ 
stances that make the skin feel smooth and soft, which is 
important to consumer acceptability. The most popular of 
this emulsifier type are "cationic" emulsifiers, which possess 
a net positive charge. The skin has a net negative charge 
because of its amino acid composition. A positively charged 
emulsifier will be attached to the skin and remain on the 
skin because of electrostatic attraction. Examples of these 
emulsifiers are behentrimonium methosulfate and dicetyldi- 
monium chloride. Cationic emulsifiers are also very effective 
when there is a need to formulate low pH emulsions (less 
than pH 4.5) as cationic emulsifiers are very stable in low 
pH environments. 

Emollients 

The choice of emollient or combination of emollients will 
have a dramatic effect on the feel, application, and delivery 
of the active to the skin. Matching solubility of active with 
the oil phase has a big effect in determining the material to 
be used. Matching the solubility parameter of an organic 
sunscreen to the solubility parameter of the oil phase has a 
significant effect on the sunscreen performance. 

The emollient category has been greatly expanded because 
of the increased use of silicones and the increasing number 
of "natural" emollients. The selection of emollient combina¬ 
tions is where art and science are combined. Selecting the 
right combination which provides the proper initial, middle, 
and end feel is one of the biggest challenges affecting the 
successful development of a cream. Concepts such as "cas¬ 
cading effect" describe this type of change which occurs as 
you apply an emollient system. 

Active ingredients 

Examples of active ingredients are sunscreen materials (e.g. 
octinoxate, titanium dioxide, avobenzone), antiacne actives 
(i.e. salicylic acid, benzoyl peroxide), skin lighteners (hyd- 
roquinone), etc. 

Humectants 

The humectant, usually a glycol or polyol, will have an effect 
on "skin cushion" and can also be part of the solvent system 
for an active ingredient. Glycols, such as propylene glycol 
and butylene glycol, are very good solvents for salicylic acid 
(an FDA approved over-the-counter active ingredient used 


to treat acne) and are frequently used for this purpose in an 
emulsion system. In addition, they also function to help with 
freeze-thaw stability. 

Thickeners 

The thickener(s) are used to control the viscosity and the 
rheology of the emulsion and can also help in maintaining 
the stability or product integrity of the emulsion, especially 
at elevated temperatures. Even in W/O creams thickeners 
are used for viscosity control. The viscosity of a cream is 
primarily determined by the thickener used and the viscosity 
of the external phase. 

The choice of thickeners, to a large extent, depends upon 
the compatibility of the thickener with the rest of the ingre¬ 
dients in the formulation, the pH of the formulation, and 
the desired feel that is trying to be achieved. 

The predominant thickeners used in O/W emulsions are 
acrylic-based polymers. The most popular materials are car- 
bomers and its derivatives. Carbomers are a cross-linked 
polyacrylate polymer and their derivatives which are high 
molecular weight homopolymer and co-polymers of acrylic 
acid cross-linked with a polyalkenyl polyether [4]. These 
polymeric thickeners are very effective in stabilizing emul¬ 
sions at elevated temperatures. (In W/O emulsions the pre¬ 
dominant thickeners for the external phase are waxes -natural 
or synthetic.) 

Water-in-oil creams 

The composition of a W/O emulsion may not look much 
different on paper than an O/W emulsion except that the 
emulsifier system would be different and would be designed 
to make a W/O emulsion. The ratio of the two phases is not 
an indication of the type of emulsion. There are many O/W 
emulsions in which the oil phase may be at a higher persent- 
age than the water phase and in a W/O emulsion the water 
phase is frequently at a higher percentage than the oil phase. 

Ointments 

There are different types of ointments. The traditional type 
of ointment contains very high levels of petrolatum as this 
material is a very good water-resistant film former and 
serves as very effective delivery system for drug actives on 
the skin. An example of a traditional petrolatum-based oint¬ 
ment is shown in Table 9.3. 

In reviewing this formulation you will notice that there is 
no antimicrobial preservative present. Some ointment for¬ 
mulations put in low levels of antimicrobial preservatives for 
added protection during consumer use, but anhydrous oint¬ 
ments are hostile environments for bacteria and are gener¬ 
ally "self-preserving." The use of an oil-soluble emulsifier 
helps with the application properties of the ointment as well 
as the ability to wash it off the skin. 

Recently, there has been an increased interest in "natural 
ointments" - ointments that do not use petrochemicals (i.e. 


73 


BASIC CONCEPTS Delivery of Cosmetic Skin Actives 


Table 9.3 An example of a traditional petrolatum-based ointment. 


Ingredients % (weight/weight) 


White petrolatum USP 

50.0-80.0 

Lanolin 

1.0-5.0 

Natural and/or synthetic waxes 

2.0-10.0 

Oil-soluble emulsifier 

1.0-3.0 

"Drug actives" 

As required 

Antioxidants 

0.1-0.5 

Fragrance/essential oils 

0.1-1.0 

Skin feel modifiers 

1.0-5.0 


Table 9.4 Atypical "natural ointment" composition. 

Ingredients 

% (weight/weight) 

Soy bean oil (and) hydrogenated 
cottonseed oil 

50.0-80.0 

Lanolin 

1.0-5.0 

Natural waxes 

2.0-10.0 

Oil vegetable-soluble emulsifier 

1.0-3.0 

"Drug actives" 

As required 

Natural antioxidants 

0.1-0.5 

Natural fragrance/essential oils 

0.1-1.0 

Natural skin feel modifiers 

1.0-5.0 


petrolatum) and are primarily based on plant-derived mate¬ 
rials. The primary difference is in the use of the material that 
replaces petrolatum in the formulation. There are a number 
of hydrogenated oil/wax mixtures that are offered and used 
as "natural petrolatums." A typical "natural ointment" com¬ 
position is shown in Table 9.4). 

"Natural ointments" generally do not have the same unc¬ 
tuous, heavy feel that petrolatum-based ointments have and 
they usually do not leave as much residual feel on the skin. 
As with petrolatum-based ointments, little or no antimicro¬ 
bial preservative is needed because of the anhydrous nature 
of the ointment. However, antioxidants are a very important 
components, as these "natural oil-based" ointments have a 
tendency to turn color and go rancid (similar to what you 
would see in a vegetable oil) without adequate protection. 


While the number of different ingredients that can be 
used in an emulsion or an ointment can sometimes seem 
overwhelming, once you break down the product into the 
attributes and benefits and esthetics that are desired, the 
choices become less daunting. 

Cream and ointment stability 

Once the formulations have been put together and evalu¬ 
ated, the next step is stability testing. This testing is carried 
out to determine what happens to the product once it is on 
the market. The ideal test would be to store the product at 
ambient temperature for 2-3 years and observe any changes 
that may occur in product integrity and determine the stabil¬ 
ity of the active ingredient(s) that are present. Because this 
timeframe is not practical, accelerated stability testing is 
conducted to predict the long-term stability of the product. 

For most emulsions, this testing involves storage of the 
finished product at 3°C, 23 °C (RT), and 40°C and some¬ 
times at 50 °C. Stability at 40°C is traditionally carried out 
for 3 months [1]. This testing is accepted by the US FDA for 
expiration dating until a full 2-3 year study is complete. Its 
purpose is not to ascertain product integrity but to establish 
the stability of the drug actives in the product. 

Elevated temperature testing (40 °C for 3 months) is con¬ 
ducted so that a determination can be made in a reasonable 
amount of time as to the integrity and stability of the product 
and to allow the product to be marketed in a reasonable 
amount of time from the completion of formulation 
development. 


Conclusions 

The development of the final formulation is a combination 
of art and science, and both have an important role in the 
use of the product by the patient or consumer. 

Once the type of formulation is determined, the ingredi¬ 
ents have been selected, the formulation developed, and the 
appropriate safety, efficacy, preservative and stability testing 
completed, the product is ready to introduce to the market. 

References 

1 Block LH. (1996) Pharmaceutical emulsions and microemulsions; 
emulsions and microemulsion characteristics and attributes. In: 
Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage 
Forms: Disperse Systems , Vol. 2. New York: Marcel Dekker, pp. 47, 
94-5. 

2 www.biology-online.org/dictionary/Ointments: Biology on Line; 
Dictionary-O-Ointments 2008. 

3 "Emulsions" presentation from Cognis Corporation, August 2004. 

4 www.personalcare.noveon.com/products/carbopol, Carbopol 
Rheology Modifiers. 


74 









Section II 
Hygiene Products 





Part 1: Cleansers 


Chapter 10: Bar cleansers 

Anthony W. Johnson and K.P. Ananthapadmanabhan 

Unilever HPC R&D, Trumbull, CT, USA 


BASIC CONCEPTS 

• There are two basic types of cleansing bar - soap bars and synthetic detergent bars. 

• Like all surfactant-based products, cleansing bars can be harsh or mild to skin. 

• Mild cleansing bars have a key role in fundamental skin care. 

• Mild cleansing bars have positive benefits for patients with skin diseases. 


Introduction 

Cleansing bars - historical perspective 

Anecdotally, soap was discovered by prehistoric man, notic¬ 
ing a waxy reside in the ashes of an evening camp fire 
around a burnt piece of animal carcass. The waxy material 
was soap. Potash from the ashes (KOH) had hydrolyzed 
triglyceride from animal fat to produce potassium soap and 
glycerol. Actual historical records show soap-like materials 
in use by Sumerians in 2500bc and there are references to 
soap in Greek and Roman records and by the Celts in north¬ 
ern Europe. As European civilizations emerged from the 
Dark Ages in the 9th and 10th centuries soap making was 
well established and centered in Marseilles (France), Savona 
(Italy), and Castilla (Spain). In those days soap was a luxury 
affordable only by the very rich. Mass manufacture of soap 
started in the 19th century and was well established by the 
turn of the century with individually wrapped and branded 
bars. 

Synthetic detergents emerged in the 20th century, pri¬ 
marily for fabric washing products. While there are many 
types of synthetic detergent, very few are suitable for 
making cleansing bars. It is difficult to make a solid product 
that is able to retain a solid form during multiple encounters 
with water and at the same time able to resist cracking, 
crumbling, and hardening when drying between uses. Soap 
is ideal for making bars but that is not to say that some 
of the early soap bars did not dry out and develop cracks 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


or become soft and mushy in humid environments. Modern 
manufacturers are able to formulate soap bars to control 
the physical behavior in use and when drying between 
uses. Soap-based bars continue to dominate the cleansing 
bar market around the world, but synthetic detergent bars 
are gaining an increasing share of market (30% of bars 
sold in the USA). 

The wide range of soap bars available in the skin market¬ 
place today might suggest a wide range of functionality but 
this is not the case. To develop new claims and gain shelf 
space in big supermarkets, manufacturers create variants by 
minor modifications of their basic bar types - the functional 
properties of soap bar variants are usually very similar - they 
all lather and they all clean. 

Formulation technology of cleansing bars 

Cleansing bars are made of surfactants that are solid at room 
temperature and readily soluble in water. While there are 
scores of commercially available surfactants only two, alkyl 
carboxylate (soap) and acyl isethionate (syndet), are used 
on a large scale for manufacture of cleansing bars (Figure 
10 . 1 ). 

These two surfactant types are quite different, leading to 
different sensory experiences for the consumer and also dif¬ 
ferences in their interactions with skin. Soap and syndet 
have in common that they have the physical properties 
required to be processed into bars that can withstand the 
challenges of use in the home. As bars they must have a 
consistent performance - they must lather easily when new 
but just as readily as the bar is used up over a period of 
weeks or months. They should produce lather quickly and 
easily and should not feel gritty in use. The rate of wear 
should be optimum, neither too fast nor too slow. They must 


77 








HYGIENE PRODUCTS Cleansers 



Sodium alkyl carboxylate (soap) 



Figure 10.1 Schematic representation of the molecular structures of 
soap (sodium alkyl carboxylate) and syndet (sodium acyl isethionate) 
showing the difference in head group structure and size. 


dry quickly after use but must not crack; they should not 
break apart if dropped, and should not absorb water and 
become mushy in a humid environment, like a bathroom. 
There are not many surfactants that can satisfy this list of 
seemingly simple practical requirements. 

Broadly speaking, there are two types of manufacturing 
process for making cleansing bars: (a) a continuous process 
of milling, extrusion, and stamping; and (b) a batch process 
of melt casting. 

Continuous processing 

The continuous process starts with synthesis of the basic 
surfactant, alkyl carboxylate, and then processing this as a 
solid through various steps during which other ingredients 
are added until the final composition is attained. After 
milling and mixing steps to ensure homogeneity, the com¬ 
pounded soap it is extruded as a continuous bar which is 
chopped and stamped into the individual bar shape of the 
final product. The technical demands of the continuous 
process impose constraints on composition and ingredient 
addition - but it is the fastest and cheapest way to make a 
cleansing bar. 

Batch processing 

The essence of the melt cast approach is to make the sur¬ 
factant and add any desired ingredients to form a hot liquid 
melt which is poured into individual bar size casts and 
allowed to set as it cools. This is a much more expensive 
process but allows for a wider range of additional ingredients 
in the product formulation. The continuous process is used 
for most of the mass market bars and the melt cast process 
for specialist bars often sold in boutiques, custom outlets, 
and department stores. 

Soap bars 

There are several major compositional types of soap bar 
with distinct bar properties and in use behaviors - speed and 
type of lather, rate of use up, aroma, skin compatibility, 
tendency for mush, etc. Most bars are either basic or super¬ 


fatted soap. Basic soaps are blends of medium chain length 
fatty acid sodium salts (Figure 10.1). Superfatted soaps are 
similar but with additional fatty acid. There are other cate¬ 
gories of soap bars based on the use of specialist ingredients: 
transparent bars, antibacterial bars, and deodorant bars. 
There are large numbers of specialist bars that are simply 
soap containing a wide range of colors, fragrances, and 
emotive ingredients such as vitamins, aloe, chamomile, and 
other natural extracts. The emotive ingredients in specialist 
bars are there to appeal to the senses and emotions with no 
real expectation that they have any detectable benefit for 
the skin. 

Basic soap 

Soap is the sodium salt of a fatty acid. As the salts of weak 
acids, soaps form alkaline solutions as they dissociate in 
water. The pH of soap is typically in the pH range 9-11. This 
is not sufficient to be overtly irritating to skin but is suffi¬ 
ciently high to negatively impact the pH-dependent proc¬ 
esses of the stratum corneum which has a natural pH of 
around 5.5. The fatty acids used in soap making are natural, 
derived from animal or plant sources, with the most common 
chain lengths in the range C12 (e.g. coconut fatty acid) to 
C18 (e.g. tallow/rendered animal fat). C12-14 soaps are 
soluble and lather easily. Cl6-18 soaps are less soluble but 
good for forming solid bars. The plant oils used in soap 
making are mostly triglycerides and when treated with lye 
and/or caustic soda they hydrolyze to the fatty acid sodium 
salts (soap) and glycerol. 

Superfatted soap bars 

Simple soaps are good cleansers but also drying to skin. Less 
drying soaps are made by adjusting the soap making process 
to leave an excess of free fatty acid in the final soap composi¬ 
tion (superfatted soaps). This excess fatty acid reduces the 
lipid stripping and drying effects of a soap bar to a small 
extent. Beauty soaps are typically superfatted soaps. 

Transparent soaps 

There are several types of transparent or semi-transparent 
soap bars. The earliest was a rosin glycerin soap bar devel¬ 
oped by Andrew Pears in 1789. The ingredients of Pears 
patented transparent soap were sodium palmitate, natural 
rosin, glycerine, water, C12 soap, rosemary extract, thyme 
extract, and fragrance. The Pears soap of today is made by 
essentially the same process, which involves dissolving the 
raw soap and other ingredients in alcohol, pouring into 
moulds followed by up to 3 months of evaporation and 
drying. 

A different type of transparent bar was introduced in 1955 
by Neutrogena based on a patented formulation invented by 
a Belgian cosmetic chemist, Edmond Fromont. His novel 
formulation was based on triethanolamine soap (in other 
words, soap where the neutralizing cation is triethanolamine 


78 







10. Bar cleansers 


instead of the usual sodium). The ingredients of the 
Neutrogena bar are triethanolamine stearate, Cl2-18 soaps, 
glycerine, water, and a range of minor ingredients including 
a little lanolin derivative and fragrance. Triethanolamine 
forms acid soaps so the pH of the Neutrogena bar at pH 8-9 
is lower than a regular soap with sodium as the cation. 

Antibacterial and deodorant soap bars 

Medicated or antibacterial soaps are a large subcategory of 
the bar soap market. These products are basic soaps con¬ 
taining one of a limited number of approved antibacterial 
agents. Some of these products are positioned as deodorant 
soap to inhibit the odor-producing bacteria of the axilla. 
Washing with any soap is effective for removing and killing 
the bacteria on skin and the value and contribution of 
added antibacterial agents is controversial. However, there 
are a variety of tests developed to assess the effectiveness 
of antibacterial soaps and there is no doubt that there is 
some deposition of the antibacterial agents on skin during 
washing and this is expected to reduce the effectiveness of 
any residual bacteria and to reduce colonization by other 
microbes. 

Non-soap detergent bars - syndet bars 

Because soap is cheap and easy to manufacture the cleansing 
bar market has remained predominantly soap bars. However, 
there has been one non-soap bar technology that has 
achieved a significant place in the US market over the last 
50 years and is now extending its reach to other regions of 
the world. This product, introduced to the US market in 
1957 as the Dove bar, is based on patented acyl isethionate 
as the surfactant component in combination with stearic 
acid which has a dual function of providing the physical 
characteristics for forming a stable bar and also acting as a 
significant skin protecting and moisturizing ingredient. The 
high level of stearic acid in the Dove bar is the basis of the 
one-quarter moisturizing cream in the product. When the 
patents for this novel technology ran out, several other acyl 
isethionate bars were introduced in the USA market includ¬ 
ing Caress, Olay, Cetaphil, and Aveeno. 

Market overview 

There are hundreds of cleansing bars on the market but 
relatively few that are widely sold. Most of the cleansing 
bar market is supplied by a small number of manufacturers 
and a limited number of brands. Figure 10.2 shows the seg¬ 
mentation of the US market for soap and syndet cleansing 
bars. 

Preservatives 

It is of interest that soap bars and syndet bars are self-pre¬ 
served in the sense that they provide a hostile environment 
for microorganisms and do not need to contain a preserva¬ 
tive to maintain product quality. 



US cleansing bars 
% total market (volume) 


Syndet 1 
Soap 1 
Soap 2 
Soap 3 

I I Soap/Syndet 
^■l Soap 4 
Syndet 2 
I I Syndet 3 
Soap 5 

l - J Private label 
Syndet 4 
Soap 6 


US syndet cleansing bars 
(% of syndet segment) 




* Less than 0.1% 
market share - 
too low to register 



Figure 10.2 Segmentation of cleansing bar market (based on average 
data for 2006, 2007, and 2008). The charts show shares (volume) for 
leading soaps and syndet bars. Brands not identified. Brands and their 
market shares vary somewhat year to year and may vary considerably 
over time. 


Impact of cleansing bars on skin structure 
and function 

Washing with soap removes dirt and grime from skin and is 
very effective for removing germs and preventing the spread 
of infection. There is an appreciation that some soaps are 
harsh and others mild, but washing with soap is so routine 
and commonplace that most people give no thought to the 
cleansing process or its impact on skin. This is a mistake. 


79 














HYGIENE PRODUCTS Cleansers 


Research over the last few years has revealed several mecha¬ 
nisms by which soap interacts with skin structures to 
adversely affect normal functioning. It is now clear that mild 
cleansing has significant benefits for both diseased and 
healthy skin. Mild cleansing can reduce the symptoms of 
common skin conditions such as eczema, acne, and rosacea 
and can enhance the attractiveness of normal skin. 

Surfactant interaction with the skin-stratum 
corneum 

As described in other chapters of this book, the outer layer 
of skin, the stratum corneum, is a very effective barrier to 
the penetration of microorganisms and chemicals unless 
compromised by damage, disease, or a intrinsic weakness 
caused by one of the genetic variations now known to 
impact the functioning of the stratum corneum. Whatever 
the normal state of the stratum corneum for an individual, 
the most challenging (i.e. potentially damaging) environ¬ 
mental factor, apart from industrial exposure to solvents and 
other harsh chemicals, is cleansing. And yet cleansing is a 
key element of good everyday skincare and there is much 
variation in the damaging potential of different cleansing 
products including cleansing bars. Understanding how 
cleansing products impact skin and knowing the mildest 
cleansing product technologies is a basic requirement for 
achieving fundamental skin care. 

Soap bar interactions with the stratum corneum 

The properties of soap that make it an effective cleanser also 
determine that it can be drying and irritating to skin. The 
high charge density of the carboxyl head group of the soap 
molecule promotes strong protein binding which is good for 
cleansing but bad for skin. Soap binds strongly to stratum 
corneum proteins and disturbs the water-holding mecha¬ 
nisms of the corneocytes. Soaps also denature stratum 
corneum enzymes essential for corneocytes maturation and 
desquamation. The result is an accumulation of corneocytes 
at the skin surface and the characteristic scaly, flaky, rough¬ 
ness associated with dry skin. 

In addition to damaging proteins, soap and other cleansers 
can disrupt and strip out the lipid bi-layers of the stratum 
corneum. The bipolar structure of the soap molecule is 
similar to the bipolar structure of the three major lipid types 
that make up the lipid bi-layers of the stratum corneum 
(fatty acids, cholesterol, and ceramides). Soap disrupts the 
bi-layer structure of these lipids in the stratum corneum and 
thereby reduces the effectiveness of the stratum corneum 
water barrier. Transepidermal water loss (TEWL) is increased 
through the leaky barrier. Also, disruption of the structured 
lipid matrix around stratum corneum cells (corneocytes) 
allows the highly soluble components of the skin's natural 
moisturizing factor (NMF), contained in the protein matrix 
of the corneocytes, to leach out. Leaching is increased by 


further cleansing or even simply by contact with water. This 
process explains the paradox that water is often a major 
factor for causing dry skin. Effects on the key lipid structures 
of the stratum corneum add to the damage caused by soap- 
protein interactions and exacerbate the development of skin 
dryness - remembering that dry skin is not simply a lack of 
moisture but a disturbance of normal stratum corneum 
function with retention and accumulation of superficial cor¬ 
neocytes. The build up of corneocytes at the skin surface is 
responsible for many symptoms associated with "dry" skin 
- scaling, flaking, roughness, dull appearance (due to light 
scattering), tightness, loss of resilience/flexibility/elasticity, 
and ultimately cracking and irritation. 

All soaps have the ability to induce dry and irritated skin 
and these effects are most evident in challenging environ¬ 
mental condition - cold or hot temperatures with low 
humidity, excessive exposure to solar UV radiation, and 
prolonged exposure to wind. The drying potential of soap 
varies according to composition such as the balance between 
soluble (C12-14) and less soluble chain lengths (C16-18) of 
the fatty acids most commonly used to make soap - the 
higher the soluble component the more drying the soap. 
Superfatted soaps are a little milder than simple soaps, and 
triethanolamine soap and glycerol bars the mildest of the 
commonly available soap bars. 

Synthetic detergent bar interactions with the 
stratum corneum 

Synthetic detergent bars (syndet bars) have been available 
on the US market for 50 years and represent a clear tech¬ 
nologic difference from soap-based cleansing bars. Nearly all 
common synthetic detergent bars are based on an anionic 
surfactant, acyl isethionate. At the time of writing (2008) 
these bars account for 40% of the cleansing bars sold in the 
USA. Alkyl glycerol ether sulfonate (AGES) and monoalkyl 
phosphate (MAPS) are two of a small number of other syn¬ 
thetic detergents that have been tried for manufacture of 
cleansing bars but none of these have been successful in the 
US market. 

Ironically, because syndet bars are shaped like soap bars 
and used for cleansing just like a soap bar, most people 
believe that synthetic detergent bars are just another variety 
of soap. Most consumers are unaware that there is a funda¬ 
mental compositional difference between soap and syndet 
bars that impacts their interactions with skin such that 
syndet bars are milder than soap bars during cleansing. 
There is a greater difference between soap and syndet 
cleansing in terms of healthy and attractive skin than most 
people realize. It is important for healthcare professionals 
and dermatologists to appreciate the difference between 
soap and syndet bars because studies show the difference in 
mildness is very relevant for their patient groups (see studies 
described below). 


80 


10. Bar cleansers 


Soap (alkyl carboxylate) and syndet (acyl isethionate) are 
both anionic surfactants and like all anionic surfactants they 
interact with skin proteins and skin lipids. But because of 
the difference in head group physical chemistry soap inter¬ 
actions are more intense leading to a higher potential for 
inducing dryness and irritation. The carboxylate head group 
is compact, leading to a high charge density that facilitates 
binding and denaturation of proteins. By contrast, the 
isethionate head group is large and diffuse, producing a low 
charge density and less ability to interact with proteins 
(Figure 10.1) 

A second and most important factor contributing to the 
mildness of the isethionate syndet bar is the ability to for¬ 
mulate acyl isethionate with high levels of stearic acid 
without losing the ability to lather. In fact, the lather is more 
dense and creamy than the lather of a typical soap bar. The 
stearic acid component of the isethionate syndet bar acts as 
a moisturizing cream and deposits on skin during cleansing, 
adding to the relative mildness of these types of bar. 


Superfatting is, in principle, a similar way to reduce the 
harshness of plain soap but the results are much more 
modest because the initial harshness of soap is higher than 
syndet and the upper limit of practical superfatting is closer 
to 10% compared to the 20-25% fatty acid that can be for¬ 
mulated in an isethionate bar. 

Another difference between soap and syndet bars is pH. 
Soap has an alkaline pH typically around pH 10-11 whereas 
isethionate/stearic acid bars are close to pH neutral with a 
pH of a little over 7. The pH of glycerol bars is in the range 
pH 8-9. These differences in pH have an effect on the inter¬ 
action of cleansing bars with the stratum corneum. Skin 
proteins swell markedly if the cleanser pH is highly alkaline 
(pH >8). Optical coherence tomography (OCT) pictures of 
stratum corneum after exposure to acidic, neutral, and alka¬ 
line pH conditions and the corresponding swelling show that 
there is significantly higher swelling in alkaline pH solutions 
(Figure 10.3). Strongly binding detergent molecules can 
increase the swelling further. 




Figure 10.3 Swelling of the stratum 
corneum in different pH buffer solutions, 
(a) Optical coherence tomography (OCT) 
images of ex vivo skin treated with 
different buffer solutions. The arrows 
show the position and thickness of the 
stratum corneum. (b) The bar chart 
provides a graphic representation of the 
same difference. 




Buffer 

* Different from pH 10 P<0.05 


(b) 


81 

























HYGIENE PRODUCTS Cleansers 


High pH also has an impact on stratum corneum lipids. 
An alkaline pH can ionize fatty acids in the lipid bi-layers 
making them more like "soap" molecules and destabilizing 
the highly organized structure of the bi-layers. 

These factors contribute to the differences in mildness of 
soap and syndet bars. Environmental scanning electron 
microscopy pictures of the skin surface and the correspond¬ 
ing transmission electron microscopy images of the protein- 
lipid ultrastructure of human skin washed under exaggerated 
conditions (nine repeat washes) with a syndet and a soap 
bar are seen in Figure 10.4. It is evident from the micro¬ 
graphs that the syndet bar washed sample exhibits well- 
preserved cells with intact proteins and lipids compared with 
the soap washed sample. 


Studies comparing mildness properties of 
soap and syndet cleansing bars 

Many consumers are not aware of the differences in drying 
and irritation potential between soap bars and synthetic 
detergent bars. In practice, most cleansing products are not 
drying to an extent that is readily perceivable and under 
normal conditions of use cleansing bars seldom produce 


irritation and inflammation. However, in other circum¬ 
stances, particularly drying environmental conditions or 
with compromised diseased skin, some cleansing bars can 
cause severe dryness and irritation. Why is this? 

Under normal conditions it is likely that the skin is super¬ 
ficially and temporarily dried by most cleansers but is rapidly 
able to restore its ability to hold moisture and maintain 
healthy functioning. However, under challenging environ¬ 
mental conditions, particularly the harsh cold winters of 
Canada and the northern USA and the hot dry summers of 
the central plains and western desert areas of the USA, 
recovery after washing is likely less rapid. Without supple¬ 
mental moisturization from the cleansing product or a skin 
cream or lotion applied after washing, a vicious cycle of 
damage and inadequate recovery is quickly established, 
leading initially to dry skin but quickly progressing to deeper 
damage with Assuring of the stratum corneum (cracking), 
deeper penetration of the surfactant, frank irritation, and 
ultimately full-thickness cracking of the stratum corneum 
leading to chapping and bleeding. This may sound extreme 
but anyone with a tendency to develop dry skin will recog¬ 
nize this scenario of raid deterioration to more severe 
irritation when the weather is drying - particularly for 
handwashing. 



Figure 10.4 Environmental scanning electron micrographs (ESEM) and transmission electron micrographs (TEM) images of human skin washed with 
water, soap, and a syndet bar (9 repeat washes). Water washed and mild syndet bar washed skin shows well-preserved lipids and plumped (hydrated) 
corneocytes. By contrast, images of harsh soap-washed skin show significant removal of lipids and damage to proteins. 


82 





























10. Bar cleansers 


The first practical demonstration that syndet bars are fun¬ 
damentally less damaging to skin than soap bars was a study 
published by Frosh and Kligman [1]. Using a new and simple 
method, the soap chamber test, they examined the skin 
irritation potential of all the cleansing bars they could pur¬ 
chase locally in Philadelphia at that time. One bar stood out 
as exceptionally mild compared with the rest of the market¬ 
place (17 other bars tested) and this was a patented alkyl 
isethionate bar called Dove. Now that the Dove patent has 
expired a number of manufacturers sell similar isethionate 
syndet bars. 

The difference in relative mildness of soap and isethion- 
ate/stearic acid syndet bars is easily demonstrated in the 
standard wash and rinse tests used by manufacturers of 
cleansing products. The forearm controlled application test 
(FCAT) and leg controlled application test (LCAT) are 5-day 
repeat washing tests. Skin condition is evaluated daily by a 
variety of techniques including visual dryness, superficial 
and deeper hydration measured instrumentally, TEWL to 


assess barrier performance, and erythema to assess irritation. 
Typical results obtained by comparing soap and syndet 
cleansers in a FCAT test are shown in Figure 10.5. 

An increase in stratum corneum dryness has a negative 
effect on the mechanical properties of the corneum. Changes 
in stratum corneum elasticity/stiffness measured in a stand¬ 
ard clinical test after washing with soap and syndet bars are 
shown Figure 10.6. While soap washing increases skin stiff¬ 
ness markedly, the milder syndet bar maintains the original 
skin condition. Such effects are magnified further under low 
humidity and winter conditions and can lead to microcracks 
in the stratum corneum and increased water loss, plus 
increased vulnerability to penetration of external chemicals 
into skin. 

Concern is sometimes expressed that industry standard 
tests are exaggerated and do not reflect real consumer expe¬ 
rience. The evidence accumulated by manufacturers and 
published in peer-reviewed journals demonstrates that 
effects in standard tests are indeed predictive of what can be 


Visual dryness 



* Syndet less dryness than all soaps 
(P< 0.05) 


TEWL 


<v 
"a> 

03 

-Q 

E 

o 


a; 

03 

c 

03 


(C) 



* Syndet sig. less barrier impairment 
than soaps 1, 2, 3, 4 (P<0.05) 


Corneometer 



(b) 


* Syndet hydrating, soaps drying 
(syndet soap differences P<0.05) 


Skicon 


:-20 


- -40- 


-60 



■ Syndet 
Soap 1 

■ Soap 2 
| Soap 3 

Soap 4 
HI TeaSoap 


* Syndet sig. less drying than 
soaps 1,2, 3, 4 (P<0.05) 


(d) 


Figure 10.5 Skin changes after 5 days of twice daily washing with soaps and syndet using the forearm controlled application test (FCAT) method, 
(a) Visual dryness; (b) transepidermal water loss (TEWL) - skin moisture barrier; (c) Corneometer - stratum corneum hydration; (d) Skicon - superficial 
stratum corneum hydration. 


83 











HYGIENE PRODUCTS Cleansers 



Figure 10.6 Changes in skin mechanical properties (stiffness) after 
5 days of twice daily washing with soap and syndet using the FCAT 
method. Soap washing induced a progressive increase in stratum 
corneum stiffness as measured using a linear skin rheometer whereas the 
syndet bar did not induce stiffness. 


Less 
dry 0 


5-day controlled 
arm wash test 


2-7 day normal use 
for daily face wash 



Practical implications of mild cleansing for 
patients with common skin disease 

The studies described in this section [2,3] were based on a 
simple hypothesis that switching patients with common skin 
diseases from their current soap bar cleanser to a milder 
syndet bar cleanser would minimize symptoms and gener¬ 
ally help in managing their skin condition. The patient 
groups studied were atopic dermatitis, acne, and rosacea. 
The results show that patient symptoms were reduced and 
general skin quality improved. 

Benefits of mild cleansing for adults and children 
with mild atopic dermatitis 

A total of 50 patients with mild atopic dermatitis were 
enrolled for a 4-week double-blind study carried out under 
the supervision of a certified dermatologist. One group of 25 
patients (19 adults and 6 children <15 years) used a mar¬ 
keted syndet cleansing bar instead of their normal cleansing 
bar for showering during the 4 weeks of the study. A second 
group of 25 patients (17 adults and 8 children) used a dif¬ 
ferent syndet bar based on the same acyl isethionate 
cleansing system. Eczema severity was measured at baseline 
and 4 weeks using the eczema area severity index (EASI) 
clinical assessment system. Other evaluations at these times 
were dermatologist assessment of non-lesional skin, hydra¬ 
tion by conductance meter, and patient self-assessment 
by questionnaire. Results indicated good compatibility with 
the syndet bar as a substitute for patient's usual bar cleanser 
for both adults and children. In addition, it was observed 
that the severity of eczematous lesions reduced with 
both bars, general skin condition was improved, and 
hydration was maintained. The main results are shown in 
Figure 10.8. 


Figure 10.7 Skin dryness induced by soap and syndet bars in a 5-day 
controlled arm wash test compared to dryness induced by 2-7 days of 
normal use once daily for facial cleansing. Arm wash test carried out on 
the same subjects as the 7-day facial wash test. Most soap users were 
unable to continue soap use for a full week. Most syndet users were able 
to complete a full week of daily face washing - dryness scores are based 
on assessments made on day 7 for the whole panel. 


experienced in normal use under realistic but challenging 
environmental conditions. Figure 10.7 shows results of a 
study where women used soap or syndet for face washing 
for a week during the Canadian winter. They were not 
allowed to use a facial moisturizer during the study. Under 
the cold drying conditions of this study the soap users rapidly 
experienced intense drying and soreness whereas the syndet 
users were mostly able to tolerate the withdrawal of their 
normal after-wash moisturizer for a week. 


Benefits of mild cleansing for acne and 
rosacea patients 

In one study, a group of 50 patients with moderate acne and 
using topical acne medications (benzamycin or benzamycin/ 
differin) were split into two treatment cells (25 patients per 
cell) and instructed to use either a syndet bar or a soap bar 
for 4 weeks in place of their normal cleansing bar. Patient 
skin condition was assessed at baseline and after 4 weeks of 
use. Although the clinical differences between soap and 
syndet in this test were not statistically significant, there was 
a clear trend that patients using soap experienced worsening 
of measures relating to skin compatibility and irritation 
during the 4-week period of the study and little or no change 
in patients using the syndet bar (Figure 10.9). 

A similar protocol was used in a study of rosacea patients. 
Seventy patients were enrolled and divided into two sub¬ 
groups for a 4-week study period. Evaluations were per- 


84 




















10. Bar cleansers 


Dermatologist clinical evaluation 
EASI (Eczema Area/Severity Index) 



* Day 28 eczema area/severity score 
sig. less than day 0 score (P<0.02) 


■ Day 0 
I I Day 28 


Patient self assessment of change in skin condition 
from day 0 to day 28 


Decreases from baseline 

Increases from baseline 

Symptom 

Change 
from day 0 

Attribute 

Change 
from day 0 


Bar A 

Bar B 


Bar A 

Bar B 

Dryness 

-1.5 

-2.1 

Complexion 

0.2 

1.3 

Itching 

-1.3 

-2.8 

Smoothness 

0.7 

2.7 

Irritation 

-1.1 

-2.7 

Softness 

0.4 

2.8 

Tightness 

-0.9 

-1.3 

Appearance 

1.3 

2.3 

Tingling 

-0.7 

-1.4 




Red numbers - sig. diff from baseline at day 28 (P<0.05) 


Figure 10.8 Changes in dermatologist and patient assessment of skin 
condition after 4 weeks' daily use of syndet cleansing bars by adult and 
child (7-15 years) patients with atopic dermatitis (AD). A total of 25 
patients used bar A and 25 used bar B. The patients were patients with 
chronic AD stabilized using a variety of treatment regimens which they 
continued during the trial. The bars were similar in composition with the 
same acyl isethionate synthetic surfactant system and different ratios of 
emollients. 


formed at baseline and at 4 weeks. The results show a similar 
trend in favor of using the syndet bar (Figure 10.9). 

The studies described above indicate a benefit of syndet 
bars for patients with disease compromised skin. Other 
studies have shown that use of syndet bars is helpful for 
skin that is compromised by treatments used to reduce the 
signs of photodamage such as retinoid therapy or chemical 
peels. 


liquid cleansing products. This is most pronounced in the 
developed markets of North America and Europe. Like 
many market trends this change is brought about by changes 
in consumer needs, habits, and attitudes. Cleansing liquids 
have become the product of choice for the shower, liquid 
soaps are increasingly used for hand cleansing, and quick 
foaming liquids, creams, and wipes have largely replaced 
soap bars for facial cleansing. Nevertheless, there is little 
doubt that cleansing bars will remain a universal household 
product for many years to come. 

This chapter describes the negative effects for skin associ¬ 
ated with cleansing and provides evidence that there are real 
benefits for patients and consumers generally to use the 
mildest bar cleansers available. It has long been recognized 
that environmental factors facilitate the drying, irritating 
actions of surfactants and that people differ in their suscep¬ 
tibility to these effects. Only recently has it become evident 
that genetic variations are direct drivers of individual varia¬ 
tions in susceptibility to develop dry and sensitive skin. It 
appears that loss-of-function mutations in the filaggrin gene 
are relatively common in humans and are the cause of mild 
and severe forms of ichthyosis vulgaris and atopic dermatitis. 
The insight that filaggrin gene mutations and variations lead 
to a compromised barrier that predisposes to dry skin is 
changing how scientists and professionals think about dry 
skin and healthy skin functioning. Some people have a good 
barrier but others are much more susceptible to environ¬ 
mental challenges - including cleansing. 

Gene profiling is not yet a routine diagnostic procedure 
but susceptibility to develop dry skin is a strong indication 
of a compromised barrier and the need for mild cleansing to 
prevent surfactant-induced exacerbation of a poor barrier. 
The future will see new and more precise diagnostic tests 
enabling dermatologists and healthcare professionals to 
more readily identify consumers and patients who have less 
than optimal stratum corneum functioning. In parallel, the 
need to identify mild products and good cleansing practice 
will come into sharper focus. It will be interesting to see if 
the future consumer product trend is a rebalancing from 
soap bars to milder syndet bars or if the trend will be a more 
direct move from bars to liquid cleansers. Most likely the 
market will develop in both directions - milder bars and 
more use of liquid cleansers. 


Conclusions 


The future of cleansing bars 

Bar soaps have been the most common product for skin 
cleansing for so long that most people never give them a 
second thought. However, since the late 1990s there has 
been a slow but steady decline in soap bar sales in favor of 


Cleansing is a basic human need and cleansing bars are the 
universal way to satisfy this need. Liquid products may be 
gaining in popularity but it will be decades before bars 
become redundant, if ever. 

Cleansing is a challenge to skin for everyone, but for 
patients with skin problems the choice of cleansing product 


85 





















HYGIENE PRODUCTS Cleansers 


Change in acne symptoms - dermatologist assessed 


~o 

o 


~G 

<V 

c 

fD 



(day 28 not statistically significantly different from day 0) 


Change in rosacea symptoms - dermatologist assessed 

0.3 “| 



(day 28 not statistically significantly different from day 0) 


□ Soap bar 
■ Syndet bar 


Figure 10.9 Dermatologist assessed changes in 
skin condition of patients with mild to moderate 
acne or mild to moderate rosacea after 4 weeks' 
use of soap or syndet bar for daily cleansing. 

In the acne study were 50 patients using topical 
benzamycin or benzamycin plus differin. In the 
rosacea study were 70 patients using topical 
metronidazole. The syndet bar was acyl 
isethionate synthetic surfactant and the soap bar 
was a standard 80/20 soap. 


is the difference between exacerbation and minimization of 
symptoms. There is ample evidence in the literature that 
syndet bars are milder than soap-based bars and better for 
patients with common dermatologic conditions such as 
atopic dermatitis, eczema, acne, and rosacea. Not everyone 
needs to use a syndet bar but many consumers and patients 
currently using soap bars could experience a practical benefit 
by switching to syndet bar. 

References 

1 Frosch PJ, Kligman AM. (1979) The soap chamber test: a new 
method for assessing the irritancy of soaps. J Am Acad Dermatol 1, 
35-41. 

2 Current Stratum Corneum Research. (2004) Optimizing barrier 
function through fundamental skin care. Dermatol Ther 17(1), 
1-68. [A full issue of the journal (9 papers) dedicated to the 
biology of the stratum corneum barrier and the impact of cleans¬ 
ing and moisturizing products.] 

3 Subramanyan K. (2004) Role of mild cleansing in the manage¬ 
ment of patient skin. Dermatol Ther 17(1), 26-34. [Specific paper 
dealing with the clinical studies.] 


Further reading 

Ananthapadmanabhan KP, Lips A, Vincent C, Meyer F, Caso S, 
Johnson A, et al. (2003) pH-induced alterations in stratum 
corneum properties. Int J Cosmet Sci 25, 103-112. 

Ananthapadmanabhan KP, Subramanyan K, Rattinger GB. (2002) 
Moisturizing cleansers. In: Leyden JJ, Rawlings AV, eds. Skin 
Moisturization. New York: Marcel Decker, pp. 405-32. 

Ertel K, Keswick B, Bryant P. (1995) A forearm controlled applica¬ 
tion technique for estimating the relative mildness of personal 
cleansing products. J Soc Cosmet Chem 46, 67-76. 

Imokawa G. (1997) Surfactant mildness. In: Rieger MM, Rhein LD, 
eds. Surfactants in Cosmetics. New York: Marcel Dekker, pp. 
427-71. 

Johnson AW. (2004) Overview. Fundamental skin care: protecting 
the barrier. Dermatol Ther 17, 213-22. 

Matts PJ. (2002) Understanding and measuring the optics that drive 
visual perception of skin appeareance. In: Marks R, Leveque JL, 
Voegeli R, eds. The Essential Stratum Corneum. London: Martin 
Dunitz, p. 333. 

Matts PJ, Goodyer E. (1998) A new instrument to measure the 
mechanical properties of human stratum corneum in vivo. J Cosmet 
Sci 49, 321-33. 


86 






10. Bar cleansers 


Meyers CL, Thorn-Lesson D, Subramanyan K. (2004) In vivo 
confocal fluorescence of skin surface: a novel approach to study 
effect of products on stratum corneum. J Am Acad Dermatol 50, 
130. 

Misra M, Ananthapadmanabhan KP, Hoyberg K, et al. (1997) 
Correlation between surfactant-induced ultrastructural changes 
in epidermis and transepidermal water loss. J Soc Cosmet Chem 48, 
219-34. 

Murahata RI, Aronson MP, Sharko PT, et al. (1997) Cleansing bars 
for face and body: in search of mildness. In: Rieger MM, Rhein 
LD, eds. Surfactants in Cosmetics. New York: Marcel Dekker, pp. 
427-71. 

Nicholl G, Murahata R, Grove G, Barrows J, Sharko P. (1995) The 
relative sensitivity of two arm-wash methods for evaluating the 
mildness of personal washing products. J Soc Cosmet Chem 46, 
129-40. 


Prottey C, Ferguson T. (1975) Factors which determine the skin 
irritation potential of soaps and detergents. J Soc Cosmet 26, 
29-46. 

Rawlings AV, Harding CR. (2002) Moisturization and the skin 
barrier. Dermatol Ther 17, 43-8. 

Rawlings AW, Watkinson A, Rogers J, et al. (1994) Abnormalities 
in stratum corneum structure, lipid composition, and desmosome 
degradation in soap-induced winter zerosis. J Soc Cosmet Chem 45, 
203-20. 

Strube D, Koontz S, Murahata R, et al. (1989) The flex wash test: a 
method for evaluating the mildness of personal washing products. 
J Soc Cosmet Chem 40, 297-306. 

Wihelm KP, Wolff HH, Maibach HI. (1994) Effects of surfactants on 
skin hydration. In: Eisner P, Berardesca E, Maibach HI, eds. 
Bioengineering of the Skin: Water and the Stratum Corneum. Boca 
Raton, FL: CRC Press, pp. 257-74. 


87 


Chapter 11: Personal cleansers: Body washes 

Keith Ertel and Heather Focht 

Procter & Gamble Co, Cincinnati, OH, USA 


BASIC CONCEPTS 

• Dry skin on the body is a particular issue for most consumers. Leave-on lotion application is not always viewed as a convenient 
intervention, so relief is sought from alternative sources such as moisturizing personal cleansing products. 

• Body washes are a relatively new introduction into the armamentarium of personal cleansing products and their use is growing 
rapidly, particularly in developed countries. 

• Body washes present unique formulation challenges and benefit opportunities compared to traditional cleansing bar forms. 

• There are several distinct types of body washes. Of these, moisturizing body washes represent the greatest departure from 
traditional personal cleaners, having the potential to improve dry skin condition. 

• Moisturizing body washes vary widely in terms of their skin effects (i.e. their ability to mitigate dryness). A product must deposit 
an effective amount of benefit agent on the skin during the wash-rinse process. Understanding the basis for a product's 
designation as "moisturizing" is key. 


Background 

Cleansing to remove soils from the skin's surface is a basic 
human need that serves both a cosmetic and a health func¬ 
tion. While cleansing needs for the face receives consider¬ 
able attention and few question the logic of specialized facial 
cleansers, cleansing needs for the body are often given little 
thought, the assumption being that any personal cleanser 
will suffice. This view is somewhat surprising given that 
body skin accounts for more than 90% of the body's total 
surface area and, as we will show, consumers have diverse 
needs and expectations from a body cleanser. 

Water alone cannot effectively remove all soils from the 
skin and surfactant-based materials have been the cleansing 
aids of choice throughout recorded history. Soap was among 
the first cleansing aids and some of the earliest references 
to soap preparation are found in Sumerian and Egyptian 
writings, although legend holds that the article we know as 
soap originated by chance at Mount Sapo in Ancient Rome 
when fat and wood ash from sacrifices were mixed with 
rainwater. 

Regardless of its origin, soap was the cleansing aid of 
choice and remained largely unchanged for centuries. The 
next real step-change in personal cleanser technology 
occurred around the time of World War I, when the first 
non-soap surfactant was introduced. However, bars contin¬ 
ued as the predominant form for body cleansing and it was 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


not until the latter part of the 20th century that liquid 
personal cleansing products for the body (i.e. body washes) 
were introduced and began to gain a foothold in some 
regions. 

Body washes are generally less messy in use than bars (e.g. 
no soap mush), are more hygienic, and offer greater potential 
to deliver skin benefits, including dry skin improvement. 
However, body washes can be less convenient to transport 
and are generally more expensive on a per use basis than 
commodity cleansing bars. As a result, body wash adoption 
tends to reflect countries' economic development status. 


Types of body washes 

Body washes currently available in the market generally fall 
into three distinct categories. Regular body washes are prod¬ 
ucts whose primary function is to provide skin cleansing. As 
such, they are typically based on a relatively simple chassis, 
although fragrance is sometimes used to define product 
character or to provide a higher order benefit (e.g. lavender 
scent may be used to produce a calming effect during use). 

Moisturizing body washes are intended to provide a dry 
skin improvement in addition to performing the base skin 
cleansing function. However, there are different ways to 
define dry skin improvement for moisturizing body washes. 
In some cases a product's benefit is judged relative to another 
(drying) personal cleanser and "improvement" amounts to 
producing less dryness than the benchmark. In other cases 
a product's benefit is judged relative to an untreated control 
and "improvement" reflects the effect of the product relative 
to the condition of untreated skin. Thus, moisturizing body 


88 







11. Body washes 


washes can provide markedly different levels of dry skin 
improvement depending on the criterion used to judge their 
performance. 

Finally, there are products that fall into a broad category 
best described as specialty body washes. These are exten¬ 
sions of regular and moisturizing body washes that contain 
ingredients intended to provide additional function or 
benefit. Examples include products that contain beads or 
other grit material (e.g. pulverized fruit seeds) to provide 
exfoliation and an enhanced dry skin benefit, and products 
that contain menthol or other sensates to provide a "cooling" 
or "tingling" sensation to the skin. 


Major formula components of body washes 

Water 

Unlike their cleansing bar counterparts, body wash formulas 
contain a high percentage of water. This situation is a dou¬ 
ble-edged sword. On the one hand, eliminating the need to 
form materials into a bar that will hold its shape while 
maintaining good performance and wear characteristics 
removes a number of formulation constraints, and this 
introduces the possibility of incorporating relatively high 
levels of non-cleanser materials (e.g. benefit agents) into the 
formulation. On the other hand, the aqueous milieu present 
in liquid cleansers and body washes introduces issues not 
present in bars. For example, many benefit agents are 
lipophilic in nature and an improperly formulated liquid 
cleaner may exhibit phase separation or creaming, not 
unlike the separation of oil and water phases that occurs in 
some salad dressings. Chemical stability is also a considera¬ 
tion; the greater mobility afforded by a liquid environment 
increases the likelihood of molecular interactions, and water 
itself can participate in decomposition reactions (e.g. hydrol¬ 
ysis). An aqueous environment also increases the potential 
for microbial contamination. Thus, formulating a liquid 
cleanser or body wash presents a number of unique chal¬ 
lenges, particularly if the product is intended to perform a 
function beyond simple cleansing such as delivering a benefit 
agent to the skin. 

Surfactants 

Surfactants are the workhorse ingredient in any personal 
cleansing product. Water is capable of removing some soils 
from the skin; however, sebum and many of the soils 
acquired on the skin through incidental contact or purpose¬ 
ful application (e.g. topical medicaments) are lipophilic in 
nature and are not effectively removed from the skin's 
surface by water alone. Surfactants, or surface-active agents, 
have a dual nature; part of a surfactant molecule's structure 
is lipophilic and part of it is hydrophilic. This structural 
duality allows surfactant molecules to localize at the inter¬ 
face between water and lipophilic soils and lower the inter¬ 


facial tension to help remove the soil. Further, surfactants 
allow water to more effectively wet the skin's surface and 
to solubilize lipopilic soils after removal, which prevents the 
soils from redepositing on the skin during rinsing. Surfactants 
are also responsible for the formation of bubbles and lather, 
which most consumers view as necessary for effective 
cleansing. 

As with cleansing bars, the surfactants used in liquid per¬ 
sonal cleansers and body washes fall into two primary 
groups: soaps and non-soaps, also known as synthetic deter¬ 
gents or syndets. Soap is chemically the alkali salt of a fatty 
acid formed by reacting fatty acid with a strong base, a 
process known as saponification. The fatty acids used in soap 
manufacture are derived from animal (e.g. tallow) or plant 
sources (e.g. coconut or palm kernel oil). These sources 
differ in their distribution of fatty acid chain lengths, which 
determines properties such as skin compatibility and lather. 
Soap's properties are also affected by external factors such 
as water hardness; soaps are generally more irritating and 
lather and rinse more poorly in hard water. Some specialty 
body washes contain soaps derived from "natural" fatty acid 
sources such as coconut or soybean oil; these products will 
behave similarly to products containing soaps derived from 
traditional fatty acid sources. 

Syndets, which are derived from petroleum, were devel¬ 
oped to overcome shortcomings associated with soaps (e.g. 
the influence of water hardness on performance) and to 
expand the pool of available raw materials used in manu¬ 
facture. Syndets vary widely in terms of their chemical struc¬ 
ture, physicochemical properties, and performance 
characteristics, including skin compatibility. Syndets are not 
necessarily less irritating than soaps. Sodium lauryl sulfate 
is an example; many dermatologists view alkyl sulfates as 
model skin irritants. Most body washes are based on syndet 
surfactant systems, and because syndets have a wide range 
of performance characteristics, most body washes combine 
several surfactant types to achieve specific performance to 
the finished product. For example, alkyl sulfates, while 
having relatively poor skin compatibility, lather well. 
Combining an alkyl sulfate with an amphoteric surfactant 
such as cocamidopropyl betaine can improve both lather and 
skin compatibility. Thus, formulating a body wash with 
syndets involves choosing surfactants to optimize perform¬ 
ance and aesthetics, balanced with cost considerations. 

Skin benefit agents 

Some body washes contain ingredients that are intended to 
provide skin benefits beyond simple cleansing. Dry skin, 
which is a pervasive dermatologic issue, is one of the most 
common benefit targets for body washes. Not surprisingly, 
moisturizing ingredients such as petrolatum, various oils, 
shea butter, or glycerin, which are found in leave-on mois¬ 
turizers, are often used in moisturizing body washes. 
However, simply including a moisturizing ingredient in a 


89 



HYGIENE PRODUCTS Cleansers 


rinse-off product is not sufficient; the product must deposit 
an effective amount of the material on skin during the 
cleansing and rinsing process. As noted earlier, standards for 
judging moisturizing efficacy differ. Clinical testing shows 
that moisturizing body washes vary widely in their ability 
to provide a dry skin benefit, and that some may actually 
worsen dryness and irritation. 

In addition to moisturizing ingredients to improve dry 
skin, body washes may also contain particulates such as 
beads or pulverized fruit seeds to aid exfoliation. A particu¬ 
late's size, surface morphology (i.e. smooth or rough), and 
in-use concentration will determine its ability to provide this 
benefit. Finally, body washes may contain ingredients that 
are intended to protect from or to reduce the effects of envi¬ 
ronmental insults. As with moisturizing ingredients, an effi¬ 
cacious amount of these materials must remain on skin after 
washing and rinsing. 

Other ingredients 

Body wash formulas contain additional ingredients that act 
as formulation and stability aids. The addition of polymers 
and salt alter a product's viscosity, which can modify per¬ 
formance characteristics or improve physical stability. Feel 
modifiers such as silicones are sometimes used to improve 
the in-use tactile properties of body washes that deposit 
lipophilic benefit agents on skin. Chelating agents such as 
ethylenediamenetetraacetic acid (EDTA) and antioxidants 
such as butylated hydroxytoluene (BHT) and are added to 
improve chemical stability, and buffering a body wash 
formula to a specific pH value can help inhibit microbial 
growth and improve the product's chemical and physical 
stability. 

Color and fragrance are an important part of the in-use 
experience for many body washes. Colors are US Food, 
Drug, and Cosmetic Act (FD&C) approved dyes and are 
usually present in relatively low amounts, so the likelihood 
of experiencing an issue with a body wash product because 
of dye is low. Fragrances are also usually present in relatively 
low amounts, although the apparent concentration may 
seem higher as a result of "bloom" that results from lathering 
a body wash on a mesh cleansing puff, the recommended 
application procedure for many of these products. The inci¬ 
dence of issues with modern fragrances is low. Some body 
washes incorporate natural oils to impart fragrance but these 
products are not necessarily without potential issues because 
some of these natural materials can cause sensitization. 


In-use performance considerations for 
body washes 

Cleansing ability 

The mechanical action associated with applying a personal 
cleanser to the body helps to loosen and remove some soils, 


but surfactants are the primary agents responsible for aiding 
soil removal, particularly lipophilic soils. However, sur¬ 
factants and the cleansing products based on them differ in 
their abilities to remove sebum and lipophilic soils [1]. These 
cleansing performance differences are a greater considera¬ 
tion in body washes than in bars because of the relatively 
lower surfactant concentrations present in the former com¬ 
pared with the latter. 

Because lipophilic soils present the greatest cleansing 
challenge, oil-based makeup materials are often used as 
model soils in tests intended to measure cleansing efficiency. 
These materials are poorly removed from the skin by 
water alone and their inherent color makes them easy to 
detect visually or instrumentally and measure on the skin's 
surface. 

To test the cleaning efficiency of various methods of skin 
cleansing, we conducted a study comparing a moisturizing 
petrolatum-depositing body wash, a syndet detergent bar, 
and water for cleansing ability. A commercial oil-based 
makeup product served as a model soil and was applied 
to discrete treatment sites on the volar forearms of 
light-skinned females. The makeup was allowed to dry for 
15 minutes and baseline colorimeter (L*) values were 
recorded at each site. Lather was generated from each 
cleansing product in a controlled manner and applied to a 
randomly assigned site for 10 seconds with gloved fingers. 
Sites were rinsed with warm water for 15 seconds, allowed 
to air dry for 30 minutes then chromameter measurements 
were repeated. Data were analyzed by a mixed-model 
procedure. 

The results show that water has little effect on removing 
the model soil from the skin and while the makeup used in 
this study is perhaps an extreme challenge, it nonetheless 
exemplifies why personal cleansing products are needed for 
soil removal. Not surprisingly, both personal cleansing prod¬ 
ucts removed a significantly greater amount of the model 
soil than did water (P < 0.01), but the petrolatum-depositing 
body wash showed significantly greater makeup removal 
(i.e. cleansing efficiency) than the syndet bar (mean AL* 
values of 5.2 and 3.2, respectively; P< 0.02). Thus, this study 
shows that a petrolatum-depositing body wash can clean 
efficiently and demonstrates that consumers are not 
restricted to the traditional bar form for their skin cleansing 
needs. 

Consumer understanding and need for 
moisturizing body washes 

Patients with dry skin that accompanies a dermatologic con¬ 
dition often require a high level of skin moisturization and 
may be willing to tolerate poor moisturizer product aesthet¬ 
ics (e.g. skin feel) to obtain relief. A recent habits and prac¬ 
tices study among a group of 558 adult females demonstrates 
that a consideration of consumers' varied moisturization 
needs and their desired product aesthetics must be made in 


90 



11. Body washes 


order to create products that improve patient compliance. 
These participants answered questions that provided a range 
of information about their needs for body moisturization 
and their expectations for a moisturizing personal cleansing 
product (i.e. body wash). 

Dry skin was a source of discomfort for a majority of par¬ 
ticipants; 62% said they were "very bothered" or "bothered" 
by discomfort due to dry skin, while 20% said they were 
"not bothered" by discomfort due to dry skin. Dry skin also 
drove these consumers to apply leave-on moisturizers; 68% 
said they "strongly agreed" or "agreed" that they needed to 
use a moisturizer every day because of their dry skin, while 
only 16% "disagreed" that their dry skin necessitated daily 
moisturizer application. With regard to moisturizing cleanser 
needs, 97% of the participants stated that they want more 
moisturization from their personal cleansing product. The 
needs fell into three groups that aligned with self-perceived 
body skin type. Women in one group (very dry skin, 32% 
of the population) want a body wash product that delivers 
a high level of moisturization and a substantial skin feel; 
women in a second group (dry skin, 33% of the population) 
want a body wash product that delivers a moderate level of 
moisturization and a somewhat perceivable skin feel; and 
women in a third group (combination skin, 22% of the 
population) want a body wash that provides a low level of 
moisturization, rapid absorption of the moisturizing agent, 
and no residual skin feel. 

This study is just one example of work conducted to 
understand female consumers' needs and expectations with 
regard to dry skin and moisturization. Traditionally, the 
needs and expectations of their male counterparts were at 
best little studied and poorly understood, or at worst assumed 
to be the same as those of females. To gain insights into male 
consumers' needs we conducted a habits and practices study 
among an adult panel representative of the US adult popula¬ 
tion comprising 303 males and 313 females. As in the study 
above, participants responded to a series of questions related 
to attitudes towards body skin condition, body skin care 
habits and practices, and attitudes towards various cosmetic 
interventions. 

This consumer research showed a strong contrast 
between the sexes in terms of their usage of products to 
care for their body skin. Males were on the whole less 
likely to use a treatment on their body than were females. 
However, dry skin ranked high on the list of body skin 
care needs for both sexes. Moisturizer application was iden¬ 
tified as the best treatment for dry skin, but males were 
less likely to apply moisturizer to their bodies than were 
females because of a perceived time constraint. Skin-feel 
parameters were also more important to males than 
females; males wanted to feel clean, not sticky or greasy. 
Surprisingly, the study results indicate that males are more 
likely to seek help from a dermatologist for their dry skin 
than females. 


Moisturization from body washes 

Dry skin on the body is a finding in many dermatologic 
conditions and the results presented in the previous section 
show that even in the absence of frank skin disease dry skin 
ranks as one of the most common body skin complaints for 
both sexes. Skin that is dry can itch, and flaking on "problem" 
areas such as legs, knees, and elbows is aesthetically unpleas¬ 
ing and can negatively impact self-confidence. Dry skin 
worsens with age, and low relative humidity, certain medi¬ 
cations, and excessive hot water exposure are among the 
factors that can exacerbate dry skin. Personal cleansing 
products are also frequently cited as agents that cause or 
worsen dry skin via removal of essential skin lipids following 
excessive cleansing or cleansing with "harsh" surfactants. 

Dry skin signals that there is an insufficient level of mois¬ 
ture in the stratum corneum. Dermatologists often recom¬ 
mend application of leave-on moisturizers to relieve 
symptoms and to provide an environment in which the skin 
can repair stratum corneum damage associated with dry 
skin. However, surveys show that a high percentage of der¬ 
matologists believe that their (female) patients do not mois¬ 
turize as recommended, a lack of convenience being cited 
as the primary reason for the perceived non-compliance. 
This pattern is consistent with the results found in our con¬ 
sumer habits and practices research. 

Coupling moisturization with an existing habit such as 
showering can improve compliance but, as noted earlier, 
there are different ways to define a moisturization or dry 
skin improvement benefit, and simply including a moistur¬ 
izing ingredient in a body wash formula does not guarantee 
that it will deposit on skin or remain in a sufficient amount 
after rinsing to provide a benefit. 

We conducted a leg wash clinical study using the industry 
standard method (leg controlled application test) comparing 
the dry skin improvement efficacy of a water control and 
three marketed moisturizing body wash products [2]. 
Treatment sites on the legs were washed in a controlled 
manner once daily for 7 days with the randomly assigned 
treatments. Expert visual scores and instrumental measure¬ 
ments collected at baseline and study end were used to 
assess the change in dry skin condition produced by the 
treatments. Expert scoring shows a range of skin effects from 
these moisturizing products (Figure 11.1). Two of the body 
washes delivered significant (P < 0.05) improvement in dry 
skin relative to the water control, while one of the products 
had little effect on visible dry skin. Skin capacitance meas¬ 
urements showed the former body washes improved stratum 
corneum hydration (P < 0.05), while the latter reduced 
stratum corneum hydration relative to the control (P< 0.05), 
i.e. it dried the skin. Expert erythema scoring and transepi- 
demal water loss (TEWL) showed a similar pattern; two of 
the body wash products improved skin condition relative to 
control, while the third significantly (P < 0.05) increased 
erythema and TEWL. This highlights the importance of 


91 


HYGIENE PRODUCTS Cleansers 



Moisturizing body wash #1 
r n Moisturizing body wash #2 
ISgl Moisturizing body wash #3 
Control 

Letters show P < 0.05 groupings 
at each evaluation 


Figure 11.1 Expert dryness scores after 7 days 
of once-daily washing with marketed body 
wash products. The results show marked 
differences in the products' abilities to provide a 
dry skin improvement (i.e. a skin moisturization 
benefit). 


understanding how products that are labeled as "moistur¬ 
izing" perform clinically whenever possible. Simply recom¬ 
mending that a patient should use a moisturizing body wash 
may not produce an optimal benefit, and the wrong product 
recommendation could actually worsen skin condition. 

The consumer research presented in the previous section 
also highlights the need for personal cleansing products that 
deliver different levels of moisturization and different use 
aesthetics. Many personal cleansers are available in versions 
that ostensibly are designed for different skin needs, but 
such products often involve relatively minor changes in 
formulation and performance. Body washes, because of the 
greater formulation flexibility they offer, provide an oppor¬ 
tunity to develop product versions that offer different levels 
of performance to meet specific needs. For example, the 
habits and practices study conducted among females identi¬ 
fied three primary consumer groups in terms of body skin 
moisturization and body wash performance needs. Various 
body wash products have been created that offer differences 
in moisturizer level and dry skin improvement benefit across 
versions in order to meet these needs. 


Who will benefit from using body washes? 

The body wash is a relatively new-to-market personal 
cleanser form that will initially appeal to users with practical 
concerns or to users seeking experiential benefits such as 
better lather and in-use scent intensity, which are often 
greater than a bar can deliver. Where body washes really 
distinguish themselves from traditional bar forms, however, 
is in their ability to provide higher order skin benefits. As 
we have shown, some body washes can provide a marked 
skin moisturization benefit that can affect not only the 
quantity but also the morphology of dry skin flakes (Figure 
11.2). A large segment of the population can benefit from 
using this type of personal cleansing product. However, the 
following are two examples of conditions that may derive a 
particular benefit from a moisturizing body wash. 


Ashy skin 

African-Americans and other dark-skinned individuals fre¬ 
quently suffer from ashy skin, a condition in which the 
skin's surface appears grayish or chalky as a result of exces¬ 
sive dryness. The condition is often exacerbated by soap bar 
use which is common among this population. Moisturizers 
or other oils can provide temporary relief but, as discussed 
earlier, convenience often limits willingness to use leave-on 
products. Petrolatum is an effective moisturizer but neat 
application to the skin is limited by both convenience and 
esthetics. However, a petrolatum-depositing body wash may 
circumvent these issues while still delivering a skin benefit. 

To test this hypothesis, we conducted a study among a 
group of 83 African-American females who normally applied 
a leave-on moisturizer to relieve their ashy skin [3]. Subjects 
used a randomly assigned syndet bar or a moisturizing 
petrolatum-depositing body wash product for daily home 
showering for a 4-week period. Endpoint evaluations 
showed that the body wash produced significantly greater 
dermatologist-scored dry skin improvement and subject sat¬ 
isfaction for items such as ashy skin improvement and 
reducing itchy/tight feeling. Perhaps most importantly, sub¬ 
jects assigned to the petrolatum-depositing body wash noted 
marked improvement in their level of satisfaction with the 
appearance of their leg skin, their level of confidence in 
letting others see their legs, and in feeling good about them¬ 
selves because of the appearance of their leg skin (Figure 
11.3). These results indicate that proper personal cleanser 
choice can not only improve the physical symptoms of dry 
skin but also impact how users feel about themselves. 

Atopic dermatitis 

Atopic dermatitis is a chronically relapsing skin disorder that 
currently affects an estimated 10% of children and adults in 
the Western Hemisphere and whose incidence is growing 
worldwide. Symptoms include xerosis, skin hyperirritability, 
inflammation, and pruritus. Personal cleansing products are 
viewed as a triggering factor for atopic dermatitis and der¬ 
matologists frequently recommend that their patients avoid 


92 

















11. Body washes 




Figure 11.2 Scanning electron microscope (SEM) photomicrographs of skin flakes adhering to tape strips taken from subjects' legs before (a) and after 
(b) using a petrolatum-depositing body wash for 3 weeks. Baseline samples show numerous large, thick, dry skin flakes; endpoint samples show fewer 
and thinner flakes. 


'I am satisfied with the ‘I am confident in letting 

appearance of my leg skin 1 others see my legs 1 




‘Based on the appearance 
of my leg skin, I feel good 
about myself 1 



I Syndet bar 
] Body wash 


Figure 11.3 Responses to psychosocial questions answered by African-American subjects before and after using a syndet bar or petrolatum-depositing 
body wash for 4 weeks. Items were rated on a +3 (strongly agree) to -3 (strongly disagree) scale. Ratings were not significantly different at baseline 
(P > 0.48); endpoint ratings given subjects assigned to use the body wash were significantly better than those given by subjects assigned to use the 
syndet bar (P < 0.01). 


93 

















































HYGIENE PRODUCTS Cleansers 


harsh cleansers. Therapy typically involves application of a 
prescription topical corticosteroid, using a mild cleanser for 
bathing or showering, and applying a moisturizer within 3 
minutes of the bath or shower to seal in moisture [4]. The 
latter suggests that a moisturizing body wash may be ideally 
suited as a therapeutic adjunct in atopic dermatitis. 

We conducted two studies among subjects undergoing 
treatment for mild to moderate active atopic dermatitis to 
examine the effect of using a moisturizing petrolatum- 
depositing body wash for cleansing. In both studies a mois¬ 
turizing syndet bar, which is often recommended to patients 
undergoing therapy, was used as a control. In one study both 
cleansers were paired with 0.1% triamcinolone acetonide 
cream. Subjects applied the topical corticosteroid as directed 
and used their assigned personal cleanser for daily shower¬ 
ing. After 4 weeks SCORAD for subjects who used the mois¬ 
turizing body wash was significantly (P < 0.01) lower than 
for subject who used the bar. Subjects using the body wash 
also noted significantly (P < 0.01) greater improvement in 
skin dryness and itching. 

The second study again involved subjects with mild to 
moderate active atopic dermatitis, but in this case subjects 
assigned to use the petrolatum-containing moisturizing 
body wash were prescribed a medium potency topical cor¬ 
ticosteroid, while subjects assigned to use the moisturizing 
syndet bar were prescribed a standard high potency topical 
corticosteroid [3]. At study end the dermatologist investiga¬ 
tor judged that subjects assigned to cleanse with the petro¬ 
latum-containing moisturizing body wash showed a 
significantly (P < 0.01) greater incidence of disease clearing 
than did subjects who used the syndet bar. The greater 
therapeutic response observed in the body wash group is 
important, but so is the fact that it was achieved using a 
lower potency topical corticosteroid, which can potentially 
reduce cost and the risk of steroid-related side effects. 
Subjects in the moisturizing body wash group also rated 
their skin condition better for a number of parameters 
related to their atopic condition. The results from both these 


studies indicate that therapeutic response in atopic derma¬ 
titis is influenced by personal cleanser choice and again 
highlight the importance of personal cleansing product 
choice when treating skin disease. 


Conclusions 

Body washes represent a new possibility in personal cleans¬ 
ing products, not only because of their ability to provide 
effective cleansing and deliver an improved in-use experi¬ 
ence (e.g. lather amount, rinse feel, scent display) compared 
with bar cleanser forms, but also because they have a poten¬ 
tial to improve skin condition by mitigating dry skin. 
Moisturizing body washes are in a position to meet a key 
consumer need for both men and women - dry skin improve¬ 
ment on the body. However, delivering a skin benefit from 
a rinse-off product is challenging and the product must leave 
an effective amount of benefit agent on the skin after 
washing and rinsing. Not surprisingly, moisturizing body 
washes vary widely in their ability to deliver a benefit and 
recommenders must understand these differences when 
evaluating moisturizing body wash products. 

References 

1 Bechor R, Zlotogorski A, Dikstein S. (1988) Effect of soaps and 
detergents on the pH and casual lipid levels of the skin surface. J 
Appl Cosmetol 6, 123-8. 

2 Ertel KD, Neumann PB, Hartwig PM, Rains GY, Keswick BH. 
(1999) Leg wash protocol to assess the skin mositurization poten¬ 
tial of personal cleansing products. Int J Cosmet Sci 21, 383-97. 

3 Grimes PE. (2001) Double-blind study of a body wash containing 
petrolatum for relief of ashy, dry skin in African American 
women. Cosmet Dermatol 14, 25-7. 

4 Hanifin J, Chan SC. (1996) Diagnosis and treatment of atopic 
dermatitis. Dermatol Ther 1, 9-18. 

5 Draelos ZD, Ertel K, Hartwig P, Rains G. (2004) The effect of two 
skin cleansing systems on moderate xerotic eczema. J Am Acad 
Dermatol 50, 883-8. 


94 



Chapter 12: Facial cleansers and cleansing cloths 

Erik Hasenoehrl 

Procter & Gamble Co., Ivorydale Technical Center, Cincinnati, OH, USA 


BASIC CONCEPTS 

• The four goals of facial cleansing are: (1) to clean skin, removing surface dirt and all make-up; (2) to provide a basic level of 
exfoliation; (3) to remove potentially harmful microorganisms (bacteria); and (4) to cause minimal damage to the epidermis and 
stratum corneum. 

• Cleansing can occur by three means: (1) cleansing by chemistry; (2) cleansing by physical action; and (3) in many cases, 
cleansing by a combination of both chemistry and physical action. 

• Chemical cleansing occurs via surfactants categorized into four primary groups: cationic, anionic, amphoteric, and non-ionic. 

• Facial cleansers can be categorized as follows: lathering cleansers, emollient cleansers, milks, scrubs, toners, dry lathering 
cleansing cloths, and wet cleansing cloths. 


Introduction 

Facial cleansing is not only a means to remove dead skin, 
dirt, sebaceous oil, and cosmetics, but also a first step in an 
overall skincare routine, preparing skin for moisturizers and 
other treatments. Facial cleansing also has an important 
role, well beyond skincare, in psychological well-being, 
helping to provide a ritualistic sense of renewal and rejuve¬ 
nation [1]. 

Many cleansing technologies - ranging from water to a 
traditional bar of soap - are available to meet the facial 
cleansing needs of different skin types and soil loads. This 
chapter provides an overview of the many specialty facial 
cleanser technologies available, discusses technologies best 
suited to each skin type and cleansing need, and provides 
an in-depth understanding of substrate-based facial cleans¬ 
ers, which represent the newest technology available for 
facial cleansing. 


History 

Facial cleansing is observed in the animal kingdom and 
existed well before Homo sapiens inhabited Earth. Early facial 
cleansing consisted primarily of a quick splash or rinse of 
the face with cold water. In fact, this habit can still be 
observed in the animal kingdom today among many pri¬ 
mates [2]. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


The first recorded use of facial cleansing utilizing more 
than water was among the Ancient Egyptians in 10 000 bc 
[3]. Egyptians were heavy users of makeups made from a 
base of metallic ores which contained natural dyes for color; 
this mixture was then painted onto the face. In this period. 
Early Egyptians typically bathed and removed makeup in a 
river. Their cleansers consisted of animal fat mixed with lime 
and perfume, and were similar to some of the homemade 
natural soaps in use today. Facial cleansing and body cleans¬ 
ing were done with the same soap. 

More recently, over the past 20 years, specialty facial 
cleansers have become quite mainstream, a result of an 
explosion in cleansing technology which has led to a multi¬ 
tude of high-quality, relatively low-cost cleansers. Most of 
the technical development have focused on three primary 
areas: 

1 Better removal of exfoliated skin, dirt, soil, excess seba¬ 
ceous oil, and makeup; 

2 Synthetic surfactants that induce less skin barrier damage 
and are thus less likely to dry skin; and 

3 Incorporation of cleansing chemistry onto cleansing 
cloths. 

Patients tend to take more care with cleaning and main¬ 
taining their face than the rest of their bodies. As such, 
consumer product companies have developed many differ¬ 
ent technologies and cleansing forms that benefit different 
facial skin types, cleansing rituals, and soil loads. Because 
there is such a broad array of cleansing forms, specialty 
facial cleansers has become a very fragmented category of 
products, which utilize more different technologies than 
most other cleaning applications. Although a wide range of 
products is available, these products share four common 
traits: 


95 







HYGIENE PRODUCTS Cleansers 


1 To clean skin (removing surface dirt and all make-up); 

2 To provide a basic level of exfoliation; 

3 To remove potentially harmful microorganisms (bacteria); 
and 

4 To cause minimal damage to the epidermis and stratum 
corneum. 

Additionally, facial cleansers are required to remove a 
myriad of chemicals and biologic materials, ranging from the 
latest waterproof makeup to excess skin oils and upper 
layers of stratum corneum. 


Function 

It is well understood that the use of harsh surfactants and/ 
or overwashing skin can result in overremoval or distortion 
of stratum corneum and intercellular lipids, which can lead 
to reduced skin barrier function [4]. 

While the wide array of facial cleanser technologies all 
provide basic levels of skin cleansing, they all clean skin 
slightly differently. The mechanisms by which cleansing is 
accomplished can be grouped into three main categories: 

1 Cleansing by chemistry; 

2 Cleansing by physical action; and 

3 In many cases, cleansing by a combination of both chem¬ 
istry and physical action. 

Chemistry of cleansing 

Two classes of chemicals are used in facial cleansers and are 
responsible for the cleaning effect: surfactants and solvents. 
Both of these types of chemicals interact with dirt, soil, and 
skin to remove unwanted material. Surfactants and solvents 
work via two different chemical mechanisms to effect 
removal of these materials. Understanding these mechanis¬ 
tic differences provides dermatologists with the insight 
needed to prescribe a cleansing regimen based on individual 
patient needs. 

Surfactants 

Surfactants or "surface acting agents" are usually organic 
compounds that are amphiphilic, meaning they contain 
both hydrophilic groups and hydrophobic groups. The 
combination of both hydrophilic and hydrophobic groups 
uniquely makes surfactants soluble in both oil and 
water. 

Surfactants work by reducing the interfacial tension (the 
energy that keeps water and oil separated) between oil and 
water by being adsorbed at the oil-water interface. Once 
adsorbed at the interface, cleaning surfactants assemble into 
a low-energy aggregate called a micelle. Surfactant needs to 
be present at high enough concentration to form a micelle, 
a level called the critical micelle concentration (CMC), 
which is also the minimum surfactant concentration required 
to clean sebaceous oil, cosmetics, etc. When micelles form 


in water, their tails form a core that encapsulates an oil 
droplet, and their (ionic/polar) heads form an outer shell 
that maintains contact with water. This process is called 
emulsification. 

Surfactants clean skin by emulsifying oily components on 
the surface of skin with water. Once emulsified, the oil can 
be easily rinsed from skin during the post wash or rinse 
process. The stronger the surfactant, the more hydrophobic 
material removed, the greater the potential skin damage 
from excessive removal of naturally occurring skin lipids, 
and the greater the ensuing compromise of optimal skin 
barrier function, therefore correct and careful formulation 
of these surfactants is required to ensure proper mildness. 
Recently marketed products show that with careful formula¬ 
tion very strong surfactants such as sodium laurel sulfate 
(SLS) can be well tolerated by skin. All surfactant-based 
cleansers require water and generally include a rinsing step. 
They are best suited to removal of oily residue. 

Unfortunately, two problems have been associated with 
cleansing with surfactants (one real and one largely folk¬ 
lore). First, because of their powerful cleansing action, 
overuse may completely eliminate the protective lipid barrier 
on the surface of skin, resulting in irritation and dryness. 
Second, for years consumers have heard negative stories 
regarding the alkaline (pH around 9) nature of these prod¬ 
ucts. Wrongly assuming that because skin pH is about 5, 
washing with these high pH surfactants can lead to an 
increase in skin pH. Recent data suggest that the skin's 
natural buffering capacity is more than adequate to 
eliminate any unwarranted impact of the pH of these 
products. 

Classic surfactants used in facial cleansers are categorized 
into four primary groups: cationic, anionic, amphoteric, and 
non-ionic. 

1 Cationic surfactants used alone are generally poorly toler¬ 
ated, and are now rarely used in skincare products without 
carful formulation into coaceravate systems. 

2 Anionic surfactants , such as linear alkyl sulfates, consist of 
molecules with a negatively charged "head" and a long 
hydrophobic "tail." Anionic surfactants are widely used 
because of their good lathering and detergent properties. 

3 Amphoteric surfactants, such as the betaines and alkylamino 
acids, are well tolerated, lather well, and are used in facial 
cleansers. 

4 Non-ionic surfactants , such as polyglucosides, consist of 
overall uncharged molecules. They are very mild (tolerated 
better than anionic, cationic surfactants on skin), but do not 
lather particularly well. 

Some surfactants are harsh to the skin while others 
are very mild. Because of the wide variety of available 
surfactants, not all surfactant-based cleansers are the 
same. It is important for patients to use products that best 
fit their skin type. Today, most cleansers use synthetic 
surfactants. 


96 



12. Facial cleansers and cleansing cloths 


Solvents 

A solvent is a liquid that dissolves a solid or another liquid 
into a homogeneous solution. Solvent-based systems clean 
skin by dissolving natural sebaceous oil and external oils 
applied to skin via cosmetics and similar materials. Solvents 
work under the chemical premise that "like dissolves like." 
Solvents can be classified broadly into two categories: polar 
and non-polar. Typical non-polar solvents used in facial 
cleansing, such as mineral oil or petrolatum, are from the 
oil family, whereas typical polar solvents used in cleansing, 
such as isopropyl alcohol and ethanol, are from the alcohol 
family. Solvent-based cleansers are usually not used in con¬ 
junction with water; rather, they are applied and then 
"wiped" off with a tissue or cotton ball. 

Solvent-based cleansers should be chosen carefully on the 
basis of cleansing need. Non-polar solvents work well for 
removing oil-based makeups and cosmetics but have little 
effect on water-based formulations. Similarly, alcohol-based 
systems work well on water-based makeups. It is also impor¬ 
tant to note that alcohol-based systems can dry skin, a 
benefit for younger consumers with acne-prone skin but a 
potential disadvantage for older consumers and those with 
dry skin. However, oil-based products can leave a greasy or 
oily residue, which is beneficial for consumers with dry skin, 
but undesirable for those with normal to oily skin types. 
Choosing a solvent-based cleanser based on skin type is 
critical. 

Physical cleaning 

An alternative to chemical cleansing is physical cleaning of 
skin. Essentially, physics, primarily in the form of friction, 
has an important role in cleansing. In facial cleansing, fric¬ 
tion is generated primarily by the direct interaction of a 
washcloth, tissue, cotton ball, or cleansing cloth and the 
surface of skin. Friction works to help dislodge soils, as well 
as increase the interaction of chemical cleaning agents (sur¬ 
factants and solvents) with soils. The role of friction is 
covered in more detail in the section on substrate 
cleansers. 


Types of facial cleansers 

Seven primary and popular forms of facial cleansers exist 
(other rarely used forms exist but are not covered in this 
chapter). These cleansers can be categorized as follows: lath¬ 
ering cleansers; emollient cleansers; milks; scrubs; toners; 
dry lathering cleansing cloths and wet cleansing cloths. Each 
form is described in detail below. A summary of cleansers, 
technologies, and uses can be seen in Table 12.1. 

Lathering cleansers 

While lathering cleansers constitute one broad classification, 
they all have one unique characteristic that separates them 


from all other cleansing forms - they all generate lather 
when used in the cleansing process. Typically, these cleans¬ 
ers are formulated with a surfactant level greater than the 
CMC such that excess surfactant can incorporate air and 
form lather. Additionally, these cleaners contain surfactants 
that have short hydrophobic chains; shorter chains enable 
faster and higher levels of lather. Most lathering cleansers 
sold today utilize synthetic surfactants that have been 
especially designed to be mild to skin. These synthetic sur¬ 
factants have little interaction with skin lipids and therefore 
produce substantially less skin damage than naturally 
derived surfactants. However, this quality also compromises 
to a small extent their capability to remove oil-soluble 
makeups. 

Many classes of surfactants are used in facial cleansers; 
two common ones include sarcosinates and betaines [5]. 
Even formulations with newer surfactants tend to exhibit 
some skin barrier damage in clinical studies. Thus, lathering 
cleansers are generally warranted for patients with normal 
to oily skin or those who are removing a high cosmetic load 
(makeup, lipstick, or other cosmetic load). Interestingly, 
there is a strong consumer bias towards lathering cleansers 
because high levels of lather provide a very strong signal to 
consumers that the cleanser is working. 

Lathering cleansers clean through the chemical process of 
emulsification, this simply means that the cleanser emulsi¬ 
fies dirt and oils, by suspending or emulsifying materials, 
thus permitting them to be removed from skin during the 
rinse process. Many formulators of lathering cleanser prod¬ 
ucts have tried to incorporate skin conditioning technologies 
that enable deposition of skin conditioners onto skin. 
Unfortunately, these technologies have generally been less 
successful at providing skin benefit ingredients than other 
cleansing forms. 

Emollient cleansers 

Emollient cleansers are a milder alternative to lather cleans¬ 
ers. Although they clean via emulsification, they do not 
form lather in the presence of water. Surprisingly, however, 
they do form a structure that suspends dirt and makeup 
within formulation. Typically, these cleansers provide a very 
high level of soil removal without drying the skin to the 
same degree as lathering cleansers. Emollient cleansers gen¬ 
erally consist of a special formulation of lathering surfactants 
in which either lathering is suppressed by an oil (e.g. mineral 
oil) or the surfactant forms a complex with another charged 
molecule to inhibit the formation of the air-water interface 
necessary to provide lather. 

Clinically, emollient cleansers are generally less harsh on 
skin than lathering cleansers. However, consumers some¬ 
times complain that emollient cleansers leave a residual film 
on skin that does not satisfy some cleansing expectations. 
Typically, these cleansers are best suited to those patients 
with high cleansing needs who also have dry skin. 


97 



hygiene PRODUCTS Cleansers 


Scrubs 

Facial scrubs are a subset of emollient cleansers. They gener¬ 
ally contain small particles of natural or polymeric ingredi¬ 
ents. Scrubs are intended to provide a deep cleansing 
experience including a higher level of skin exfoliation from 
abrasion with the particles. A non-exhaustive list of natural 
scrub particles includes seeds of many fruits (e.g. peach, 
apple, apricot), nut shells (e.g. almond, walnut), grains (e.g. 
oats, wheat), and sandlewood. Synthetic scrub particles 
include polyethylene or polypropylene beads. Because of 
their abrasive nature, patients with sensitive skin may not 
want to use these as their daily use cleanser; for those with 
sensitive skin they should be used once or twice a week in 
addition to normal cleansing routines. 

Cleansing milks 

Milks are a form of cleaner that is generally not used in 
conjunction with water. Because they are not used in con¬ 
junction with a water rinse, cleansing milks are ideal for 
depositing beneficial agents, such as humectants, petrola¬ 
tum, vitamins, and desquamatory ingredients, onto the skin. 
These cleansers are a good choice for cleaning dry or other 
diseased skin. One drawback is that the residual ingredients 
left on skin can make skin feel as though cleansing is incom¬ 
plete. Milks work by dissolving, as opposed to emulsifying, 
oils and dirt. Typically, they are applied like a lotion and then 
wiped off with a tissue, cotton ball, or towel. 

Toners 

Toners are a class of facial cleansers formulated to clean skin 
and shrink pores. This class of cleanser utilizes solvency as 
the primary mode of cleaning. Toners are usually applied 
with a physical substrate, such as cotton balls, tissues, or 
wash cloths; however, some newer toners can be sprayed 
on and wiped off. In most cases, toners are used in the 
absence of water. Toner formulations generally utilize alcohol 
as the solvent of choice and some level of humectants. 
Toners usually exist in three strengths: 

1 Mild: 0-10% alcohol, refresher; 

2 Medium: 10-20% alcohol, tonic; and 

3 Strong: 20-60% alcohol, astringent. 

More recently, some companies have developed two-phase 
toners, which consist of a solvent and an immiscible oil 
formulated to provide astringent benefits while minimizing 
the dry skin feeling. Typical uses of toners are makeup 
removal and pore cleaning associated with acne care. Toners 
are popular with teenagers and young adults because of the 
perceived acne benefits and pore tightening associated with 
this technology. 

Substrate cleansers 

Over the years, facial cleansers have evolved from tradi¬ 
tional bar soaps, to milder synthetic detergents, and, most 
recently, to cleansing cloths (disposable substrates such as a 


non-woven material) pretreated with active cleansing and 
conditioning ingredients. Introduced in the early 2000s, 
substrate-based cleansers are a relatively new addition to the 
cleansing technologies available to dermatologists and con¬ 
sumers. These cleansers combine low levels of mild deter¬ 
gents with conditioning ingredients to provide state-of-the-art 
cleansing and exfoliation with unprecedented mildness [6]. 
Further, cleansing cloths can be designed to meet the specific 
needs of different skin types. 

The substrates used in cleansing cloths generally consist 
of natural fibers (e.g. cotton); synthetic fibers (e.g. rayon, 
polyester terphalate [PET] or polypropylene); or a blend of 
one or more of these fibers. Depending upon the fibers used 
and the non-woven manufacturing process, the substrate 
texture can be tailored to meet differing expectations from 
very soft to rough, meaning that different exfoliation levels 
can be delivered to the consumer. Technology introduced 
in 2007 further improves exfoliation and cleansing capabili¬ 
ties by printing a polymer on the surface of a non-woven 
cloth. 

The mechanism by which cleansing is accomplished with 
a cloth is different from that with the liquid cleansers 
described above. In the case of substrate cleansers, cleaning 
is driven by a combination of physics (friction from interac¬ 
tion with cloth and skin) and chemistry (either emulsifica¬ 
tion or dissolution). This combined action offers several key 
advantages for product formulation and use. Because of the 
form itself, the cloth can contain a low level of surfactants. 
Further, utilizing multiple cleansing mechanisms allows 
formulators the flexibility to customize formulations that 
contain smaller amounts of chemical ingredients. As a 
result, substrate-based cleansers can be formulated with as 
little as 25% of the surfactant used in traditional liquid 
cleansers (P&G Beauty, Cincinnati, OH, USA, Comparison 
of surfactant level in Olay Foaming Face Wash, and Olay 
Daily Facials; unpublished data). For the patient, use of 
products with combined cleaning mechanisms results in 
much cleaner skin. Also, lower surfactant levels translate to 
less skin damage. (True when directly comparing skin 
damage versus surfactant level of identical surfactants. 
Surfactant type alone has a large impact on skin damage 
and must be considered as well as surfactant level when 
recommending a cleanser.) Another key trait of substrate 
cleansing cloths is that dirt, makeup, and oil are picked up 
by and contained within the cloth. The visible dirt and oils 
on the cloth provide a subtle clue to patients that the cleans¬ 
ing step is complete, reducing overcleansing, another con¬ 
tributor to skin damage. 

Despite the low level of surfactants in substrate cleansers, 
these products can still generate a generous lather via the 
cloth structure, which incorporates air as the lather is gener¬ 
ated. The low levels of mild detergent combined with the 
ability to deposit conditioning agents directly onto the skin 
result in improvement in the skin's overall condition beyond 


98 


12. Facial cleansers and cleansing cloths 


basic cleansing. Finally, the different cloth textures allow 
individualized, but gentle, exfoliation which removes skin 
flakes for a more even skin surface. This combination of 
benefits can eliminate the need for other specialty cleansing 
products such as toners and exfoliators. Two popular forms 
of substrate-based cleansers exist today: 

1 Dry cleansing cloths; and 

2 Wet cleansing cloths. 

The mechanism by which cleansing is accomplished with 
a cloth is different from that with the liquid cleansers 
described above. In the case of substrate cleansers, cleaning 
is driven by a combination of chemistry (either emulsifica¬ 
tion or dissolution) and physics (friction from interaction 
with cloth and skin). This combined action offers several key 
advantages for product formulation and use. Utilizing mul¬ 
tiple cleansing mechanisms allows formulators the flexibility 
to customize formulations that contain lower levels of chem¬ 
ical ingredients. As a result, substrate-based cleansers can be 
formulated with as little as 25% of the surfactant used in 
traditional liquid cleansers [7]. For the patient, use of prod¬ 
ucts with combined cleaning mechanisms results in much 
cleaner skin. Also, lower surfactant levels translate to less 
skin damage. Another key trait of substrate cleansing cloths 
is that dirt, makeup, and oil are picked up by and contained 
within the cloth. The visible dirt and oils on the cloth 
provide a subtle clue to patients that the cleansing step is 
complete, reducing overcleansing, another contributor to 
skin damage. 

Dry lathering cleansing cloths 

In early 2000, the advent of daily cleansing cloths ushered 
in the next generation of facial cleansers. Dry cleansing 
cloths consist of lathering surfactants that have been incor¬ 
porated in the manufacturing process onto a disposable 
wash cloth. The patient is instructed to wet the cloth at 
the sink with warm water and mb to generate lather. 
Therefore, these products provide a rich, creamy lather like 
one would find in the lathering cleansers described earlier. 
Additionally, many of these products contain and deposit 
on to stratum corneum moisturizing ingredients such as 
petrolatum and glycerin. These products became an instant 
success because they combine multiple skin care benefits 
into one product: 

1 High level of cleansing; 

2 High level of exfoliation; 

3 Minimal reduction in skin barrier function; 

4 Rich lather; and 

5 In the case of at least one product, significant moisturiza- 
tion [6]. 

A unique advantage of dry cleansing cloth technology is 
that the product can be manufactured so that different 
ingredients can be placed in different "zones" on a cloth. 
This simple approach enables skilled formulators to use 
ingredients that are not compatible in a liquid cleanser. Olay 


Daily Facials is one example in which the cleansing sur¬ 
factant, skin conditioner, and fragrance are applied sepa¬ 
rately and to different zones of a cloth. This permits the 
product to deposit conditioning ingredients directly onto 
skin during the washing procedure, thus delivering unprec¬ 
edented conditioning benefits from a lathering cleanser. 
In fact, cleansing cloths are the only specialty cleansing 
technology that is proven to provide the cleanest skin 
and improve skin barrier function. Studies have shown 
that separate addition of petrolatum onto a cleansing cloth 
provided unparalleled hydration and transepidermal water 
loss (TEWL) benefits and resulted in a smoother skin surface, 
a more compact stratum corneum, and well-defined lipid 
bilayers at the surface of the stratum corneum [8]. 

Wet cleansing cloths 

Wet cleansing cloths are traditionally manufactured and 
shipped to the consumer in their wet state. They originated 
from disposable wipes technology that was initially devel¬ 
oped for removal of excrement and other soils from babies 
during diaper changes. Wet cloths are used without addi¬ 
tional water in both the cleaning and rinsing (wiping off) 
rituals. Wet cloths are generally of the non-lathering variety 
and as such can be used as a "wipe-off" product, as opposed 
to being rinsed with water. The advantage of wet cloths is 
that small amounts of beneficial ingredients, such as humect - 
ants and lipids, are left behind on the skin. This property 
makes wet wipes one of the most effective cleansing prod¬ 
ucts for patients with dry skin. 


Guide to selecting facial cleansers 

Recommending a facial cleansing regimen can be a daunting 
task given the multitude of cleansing forms available. To 
choose the most appropriate cleanser, physicians should 
consider skin type, skin problems, and any skin allergies. 

The following section provides a short reference guide and 
tools to help in selection of cleansers based on patient skin 
type, cleansing need, and preference. The selection guide is 
broken into three parts or strategies: 

1 Selection based on skin type; 

2 Selection based on cleansing form; and 

3 Selection based on skin problems. 

Selection based on skin type 

The first step in selecting a facial cleanser is to assess the 
patient's skin type and to categorize it as dry, oily, or 
normal. Once skin type has been determined, assess the 
skin for any problems, such as acne, excessive flakiness, 
and dryness. Table 12.1 systematically lists the main facial 
cleansers covered in this chapter, and highlights the key 
characteristics of each cleanser and the best cleanser for 
each skin type. 


99 



HYGIENE PRODUCTS Cleansers 


Table 12.1 Cleanser technology and skin types. 

Type of facial cleanser 

Primary cleaning mechanism 

Key characteristics 

Primary recommended 
skin type 

Liquid lathering cleansers 

Emulsification 

Forms lather when wet 

Oily 

Emollient cleansers 

Emulsification 

Non-lathering 

Dry 

Scrubs 

Emulsification 

Non-lathering, particulates provide 
exfoliation benefit 

Dry, f la key 

Milks 

Dissolution 

High conditioning, generally not 
used with water 

Dry skin 

Toners 

Dissolution 

Low viscosity liquid, pore tightening 

Oily/you ng 

Acne prone 

Dry cleansing cloths 

Emulsification and physical removal 

Provides multiple benefits: cleansing, 
conditioning, exfoliating, toning 

All skin types 

Wet cleansing cloths 

Dissolution and physical removal 

Provides multiple benefits: cleansing, 
conditioning, exfoliating, toning. 
Generally not used with water 

Dry skin 


Cleanser form 


o 

o 

Dry cleansing cloth 

0 Toner 

Wet cleansing cloth 


o 


Milk 


o 

Emollient 


o 

Scrub 

o 


Lathering 



Lathering ■ » Non lathering 


Figure 12.1 One of the main cleansing ritual preferences: no substrate/ 
substrate and lathering/non-lathering. 


Selection based on cleanser form or 
cleansing ritual 

The second strategy for selecting facial cleansers is to first 
assess a patient's cleansing ritual preference. Figure 12.1 
depicts one of the main cleansing ritual preferences: no 
substrate/substrate and lathering/non-lathering. To use this 
approach most effectively, first, identify the quadrant of 
Figure 12.1 that best describes the patient's ritual preference, 
and then use Table 12.1 to select a facial cleanser that best 
matches the patient's skin type. This may be the best 


Cleansing (sebaceous oil) 


o 

Emollient 


Milk 


Scrub Lathering 

cleanser 

Wet wipe 


o 

Toner 

(alcohol-based) 

o 

Dry wipe 


Poor 


Excellent 


Figure 12.2 Products for the removal of excess sebaceous oil. 


approach to selecting a cleanser is when compliance with 
skincare is critical. 

Selection based on skin problems 

In many cases, cleanser selection may be somewhat subjec¬ 
tive. The following figures provide a hierarchy of the primary 
benefits associated with facial cleansers ranked by cleanser 
type. The benefits described in this section are cleaning 
excess sebaceous oil, cleaning dirt and makeup loads, exfo¬ 
liation, and mildness to skin. Considering these benefits 
when prescribing a cleansing routine may prove useful in 
providing a cleanser that fully meets patient expectation and 
needs. 

Cleaning excess sebaceous oil 

Removal of excess sebaceous oil is a significant concern of 
teens and young adults. Cleansing of sebaceous oil is best 
accomplished with either lathering products that emulsify 
the oils or toners that are specifically formulated to solubilize 
sebaceous oil. These products and can also give users a sense 
of control over oily skin by providing pore tightening ben¬ 
efits (Figure 12.2). 


100 













12. Facial cleansers and cleansing cloths 


Cleaning dirt and makeup 

One of the primary benefits of a facial cleanser is removal 
of high makeup loads and dirt. By a wide margin, dirt and 
makeup removal is best performed by substrate cleansers. 
The high cleansing capability of these cleansers is brought 
about by their capability to provide both physical and chemi¬ 
cal cleaning, in addition to the substrates' ability to trap and 
hold dirt and oil within their fibers (Figure 12.3). 

Exfoliation: removing dry, dead skin cells 

When high exfoliation is required, because of aging or for 
other reasons, products that provide physical cleansing are 
an appropriate choice because they also provide the highest 
level of exfoliation. Exfoliation is brought about by physical 
abrasion, which removes the top layers of skin. As a side 
note, most cleansers provide low to insignificant levels of 
exfoliation; thus, if exfoliation is the main skin need, a 
substrate-based cleanser is highly recommended (Figure 
12.4). 

Cleanser mildness 

For much of facial cleansing history, cleanser mildness was 
a significant concern. Now, with new surfactant and cleans¬ 
ing technologies, most specialty facial cleansers (with the 
exception of toners) provide close to neutral or better mild¬ 
ness. Figure 12.3 ranks cleansing forms for skin for patients 
for whom dry skin is a key complaint. 


Conclusions 

Many different facial cleansing forms exist today. All can be 
categorized on the basis of three factors: 

1 The type of chemistry used, either surfactant or solvent 
based; 

2 Whether or not the cleansing form creates lather; and 

3 Whether or not the cleansing form incorporates physical 
cleansing as well as chemical cleansing. 

All of these facial cleansing forms provide the basic level 
of cleansing required to maintain healthy skin; however, 
different skin types benefit from different cleansing forms, 
and patient preference drives usage and compliance. 

The future of the facial cleansing category is bright. 
Significant innovation is expected to continue for the fore¬ 
seeable future, particularly in substrate cleanser applications 
and formulations for removing the new and more durable 
makeups and mascaras that are entering the market. 
Technical development will continue to focus on low damage 
to skin and improved delivery of specially directed skin 
ingredients during the cleansing process. 


Cleansing (makeup) 


o 

o 

Toner (for non¬ 

o 

Scrub 

waterproof makeup) 

Dry wipe 

o 

o 

o Emollient 

o 

Lathering 

Wet wipe 

Milk 

cleanser 



Poor ► Excellent 


Figure 12.3 Products for the removal of dirt and makeup. 


Exfoliation 


o o 

Milk Lathering cleanser 

o 

o 

Scrub 

o 

Wet wipe 

o 

Emollient 


Dry wipe 

o 



Toner 



Low 


—► High 


Figure 12.4 Products for the removal of dry, dead skin cells. 


Mildness/conditioning 


o 


o 

Toner 

o 


Dry wipe 

Scrub 


o 

Emollient o 


o 

Wet wipe 


Lathering cleanser 

Milk 


Low High 


Figure 12.5 Products for patients for whom dry skin is a key complaint. 

References 

1 Zhong C-B, Liljenquist K. (2006) Washing away your sins: 
threatened morality and physical cleansing. Science 313(5792), 
1451-2. 

2 Bolles RC. (1960) Grooming behavior in the rat. J Comp Physiol 
Psychol 53, 306-10. 

3 Nicholson PT, Shaw I. (2000) Ancient Egyptian Materials and 
Technology. Cambridge UK: Cambridge University Press. 

4 Ananthapadmanabhan KP, Moore DJ, Subramanyan K, Misra M, 
Meyer F. (2004) Cleansing without compromise: the impact 
of cleansers on the skin barrier and the technology of mild 
cleansing. Dermatol Ther 17, 16-25. 

5 Paye M, Barel AO, Howard I. (2006) Handbook of Cosmetic Science 
and Technology , 2nd edn. Informa Health Care. 

6 Kinderdine S, etal. (2004) The evolution of facial cleansing: sub¬ 
strate cleansers provide mildness benefits of leading soap and 
syndet. P&G Beauty Science poster presentation, 62nd Annual 
Meeting of the American Academy of Dermatology, February 
6-11, 2004. 

7 McAtee D, etal (2001) US patent 6280757 8-28-2001 

8 Coffmdaffer T, et al. (2004) Assessment of leading facial skin 
cleansers by microscopic evaluation of the stratum corneum. P&G 
Beauty Science poster presentation, 62nd Annual Meeting of the 
American Academy of Dermatology, February 6-11, 2004. 


101 







Chapter 13: Non-foaming and low-foaming cleansers 

Duncan Aust 

DFB Branded Pharmaceuticals, Fort Worth, TX, USA 


BASIC CONCEPTS 

• Effective cleansing can be achieved without foam production. 

• Non-foaming and low-foaming cleansers are appropriate for all skin types. 

• Mild surfactants are key to minimizing barrier damage. 

• Non-foaming and low-foaming cleansers are typically water-based. 


Introduction 

The effective and appropriate use of a suitable skincare 
regimen is critical to maintaining healthy skin. This cleans¬ 
ing regimen becomes more important in dermatologic 
disease, where an inappropriate skin care regimen can 
impede positive treatment outcomes [1]. Cleansing is the 
first step in managing any dermatologic disease and the right 
choice of cleanser can have a considerable impact on treat¬ 
ment success. 

The earliest cleansers were used by the Babylonians 
around 2200 bc. The Egyptians subsequently combined 
animal and vegetable oils with alkaline salts to create soap- 
like substances. Cleansers then evolved to contain salts of 
fatty acids derived by reacting fat with lye in a process 
known as saponification, which marked the beginning of 
currently available foaming soap-based cleansing systems. 

Non-foaming cleansers were developed in the 2nd century 
in the form of cold creams and milks. The Greek physician 
Galen is considered the father of cold cream, because he 
combined olive oil, beeswax, water, and rose petals. More 
modern formulations also add borax. 

There are now many different classes of cleansers; 
however, this chapter focuses on non-foaming and 
low-foaming cleansers. It outlines the different types of 
non-foaming cleansers and how they vary from their 
regular foaming, liquid, or bar counterparts. It also outlines 
the most logical choice of non-foaming or low-foaming 
cleansers for certain skin types and discusses the merits of 
various cleanser formats. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Types of non-foaming and low-foaming 
cleansers 

Many consumers mistakenly believe foaming or lathering is 
a requirement for effective cleansing. However, what is not 
broadly understood is the fact that, even in the absence of 
foaming, cleansing can still occur. This is the fundamental 
premise upon which non-foaming and low-foaming cleans¬ 
ers are based. 

There are two primary classes of non-foaming and low- 
foaming cleansers: aqueous or water-based formulations, 
which may or may not require water for cleansing, and a 
second class of waterless cleansers. The majority of non¬ 
foaming and low-foaming cleansers are water-based formu¬ 
lations containing several ingredients: water, surfactants, 
moisturizers, stabilizing agents, preservatives, fragrances, 
and dyes (Table 13.1). Key to the efficacy of these aqueous- 
based cleanser formulations are three primary ingredients; 
water, surfactants, and humectants. 

Surfactants 

The most important ingredient in the majority of cleansing 
systems is the surfactant. A surfactant is a chemical that 
stabilizes mixtures of oil and water by reducing the surface 
tension at the interface between the oil and water molecules 
and enhances the formation of foam and its colloidal stabil¬ 
ity. Surfactants perform two functions in a cleanser. First, 
they stabilize the cleanser formulation by allowing the oil 
phase and water phase to coexist in a stable system. Without 
surfactants, it would be impossible create single-phase for¬ 
mulations. Second, and most importantly, surfactants are 
required to meet the performance requirements of the 
cleanser. 

Surfactants can generally be divided into five classes: 
anionic, amphoteric (zwitteronic), cationic, non-ionic, and 


102 







13. Non-foaming and low-foaming cleansers 


Table 13.1 Types of non-foaming and low-foaming cleansers. 

Cleanser types 

Physical forms 

Key ingredients 

Foaming 

Lotions 

Bars 

Body washes 

Surfactants, water, foam boosters, 
humectants, preservatives 

Surfactants, waxes, binders, filers 

Surfactants, water, foam boosters, 
humectants, preservatives, dyes 

Low foaming 

Lotions 

Gels 

Creams 

Surfactants, water, humectants, preservatives 
Surfactants, water, humectants, preservatives 
Surfactants, water, humectants, preservatives 

Non-foaming 

Cold creams 

Waterless cleansers 

Thin lotion/milks 

Two phase 

Water, oil, wax, surfactants 

Solvent/alcohol, water, surfactant 

Water, moisturizers, oils, surfactants, 
solvents, preservatives 

Oil, water, solvent/alcohol, dyes 


polymeric surfactants. The anionics are characterized by 
their good foaming and cleansing abilities, but can be too 
irritating for the skin. As a result, anionics are combined 
with milder surfactants or conditioning agents. Non-ionics 
and polymeries tend to be the mildest surfactants and are 
used in "gentle" cleansing systems. Traditional cationics 
can be irritating, but new classes have been introduced, 
rivaling the performance of the non-ionics. The final class, 
amphoterics, are also mild but this property can differ 
with pH. 

Over the last 40+ years, there has been an effort to develop 
"gentler acting" surfactants, hence the large number of non¬ 
ionic surfactants currently available. The non-ionic sur¬ 
factants are the basis for a new group of low-foaming, 
reduced irritation cleansers and may be combined with the 
polymeric or amphoteric classes. Examples of mild sur¬ 
factants and surfactants with low irritation include sulfoac- 
etates, acyl sarcosinates, amphoproprionates, alkanolamides, 
alkylglucosides, and the original mild surfactant cocamido- 
propyl betaine. 

Low foam production 

A major drawback of most mild synthetic surfactant systems 
is poor lather performance. Generally, the longer the carbon 
backbone of the surfactant, the less irritating the molecule. 
However, this mildness is often obtained at the expense of 
effective cleansing and lathering. In fact, many modern 
cleansers supplement their formulations with "foam boost¬ 
ers" simply to enhance the appearance of foam. These addi¬ 
tional ingredients are not required for cleansing, have no 
cleansing properties, and are there solely to meet consumer 
expectations. A careful balance is required between mildness 
and lather. 


Mildness 

The potential for irritation can be reduced by appropriately 
matching surfactants. For example, sodium lauryl sulfate 
(SLS), an anionic surfactant with a high index of irritation, 
has been shown to elicit less irritation when combined with 
sodium laureth sulfate (SLES) [2]. Balancing the level of 
surfactants in the formulation to ensure effective cleansing 
while not having a detrimental effect on skin barrier lipids 
and proteins is important. 

Other ingredients can be added to the cleanser formula¬ 
tions to mitigate any detrimental effects. Some of the milder 
cleansers contain humectants, such as glycerin, to attract 
water to the skin. Other humectants, such as butylene glycol 
or propylene glycol, have been used but are less favored 
than glycerin. Hyaluronic acid, which has the capacity to 
bind many times its own weight in water, is very expensive 
and seldom used. The use of humectants in low-foaming 
and non-foaming cleansers is now commonplace in high 
end products. 

In addition to humectants, other skin barrier building 
ingredients can be used. For example, ceramides and plant 
extracts with reported antioxidant, anti-irritant properties 
can be used. However, it is challenging to ensure that these 
ingredients are delivered to the skin in a cleanser that is 
rinsed away. Utilizing controlled or sustained release systems 
can increase ingredient delivery. One example of a control¬ 
led release delivery system employed in a cleanser system is 
the use of a multivesicular emulsion. This emulsion is com¬ 
posed of multilamellar particles, which allow for the sus¬ 
tained release of substances such as ceramides, glycerin, and 
hyaluronic acid [3]. 

The mildness of a cleanser is dependent upon many 
important factors, most notably the choice of other 


103 





HYGIENE PRODUCTS Cleansers 


Table 13.2 Principal cleanser types. 

Cleanser types 

Advantages 

Disadvantages 

Skin type best suited 

Non-foaming 

Gentle 

Non-drying 

Low levels of surfactants 

Limited cleansing ability for oily types 

Limited rinsibility with cold creams 

Can leave behind residue 

Dry to normal 

Low foaming 

Gentle 

Non-drying 

Easy to remove 

Low levels of surfactants 

Limited cleansing ability for oily types 

Dry to normal 

Bar 

Excellent cleansing ability 

Can strip barrier of essential oils and lipids 

Drying 

Can raise pH of skin 

Primarily composed of anionic surfactants 

Oily 

Foaming liquid 

Good cleansing ability 

Easy to remove 

Can strip barrier of essential oils and lipids 

Normal to oily 


ingredients in the formulation and the product's pH [4,5]. 
Two of the most irritating classes of ingredients used in 
formulations are fragrances and preservatives. Often the 
combination of fragrances and high levels of surfactants 
gives way to a high irritation index. Several studies have 
correlated a product's poor performance in patch testing 
experiments to the combined effects of surfactants and 
allergens [6,7]. Because of these effects, mild cleanser 
products are fragrance free; however, preservatives remain 
a necessary part of the formulator's arsenal to ensure the 
products remain free from microbial contamination. 

Waterless cleansers 

Other means of skin cleansing not involving traditional sur¬ 
factants is with the use of solvents to dissolve oils and sebum. 
These waterless facial cleansers are aqueous-based alcoholic 
preparations, typically containing diluted isopropyl alcohol 
and a small amount of surfactant. Sebum is soluble in 
alcohol and glycol-based solvents. These cleansers are con¬ 
venient to use without access to water, and can be effective 
in patients with very oily skin; however, long-term usage 
may be harmful to the skin barrier. 

Other alternative cleansing systems include two-phase 
systems, where the oil and water-solvent phase do not mix 
in the formulation and remain as two distinct layers. These 
systems are mixed by shaking prior to use. They have the 
advantage of low surfactant concentrations but do not have 
broad consumer acceptability. 

Lipid-free cleansers 

A new class of cleansers for normal to oily skin is referred 
to as a lipid-free cleanser. Lipids are defined broadly as fat- 
soluble, naturally occurring molecules, such as fats, oils, 


waxes, sterols, monoglycerides, diglycerides, and phospholi¬ 
pids. Lipid-free cleansers have the advantage of not deposit¬ 
ing any lipid-like materials on the skin surface. They balance 
their cleansing and moisturizing ability. In lipid-free cleans¬ 
ers, moisturization is performed by replacing sebum with 
synthetic oils along with the addition of humectants, such 
as glycerin. While good for normal to oily skin, lipid-free 
cleansers may not be the ideal choice for dry skin. Table 13.2 
highlights the principal cleanser types: bar, foaming liquid, 
non-foaming, and low-foaming (regular and lipid free). 


Mechanisms of cleansing 

In the case of the non-foaming cleansers, especially cold 
creams, the primary mode of action is dependent on the 
formulation's ability to bind sebum, dirt, bacteria, and dead 
skin cells. Cold cream formulations are water-in-oil emul¬ 
sions (W/O) where the external phase of the emulsion is the 
hydrophobic or oily component and the water is partitioned 
as small droplets in the internal phase. It is because of the 
external oil phase that cold creams bind well to sebum, dirt, 
and cosmetics with easy removal by wiping. 

Certain lighter lotions or milks also work along a similar 
principle, although they differ from cold creams because 
they are primarily oil-in-water (O/W) emulsions. Upon 
application to the skin surface, the oil phase droplets "seek 
out" sebum on the surface of the skin, entrapping it, and 
facilitating its removal with gentle wiping or water rinsing. 
These lighter lotions also differ from cold cream by contain¬ 
ing some classic surfactants. The surfactants are used to 
maintain a stable emulsion with an internal oil phase and 
external aqueous phase, but do not provide any foaming 


104 






13. Non-foaming and low-foaming cleansers 


capability. These cleansers have limited cleansing ability and 
are not the most effective class of cleansers for oily skin, but 
work well on dry to normal skin. 


Cleansing skin barrier damage 

The cutaneous effects of surfactants are dependent upon the 
type, duration of exposure, and concentration [8,9]. Many 
different surfactants affect the stratum corneum, or outer 
layer of the epidermis, causing dryness, damage to the 
barrier function of the skin, irritation, itching, and redness 
[10]. Surfactants interact with various components of the 
stratum corneum, including proteins and lipids. Interaction 
occurs with corneocytes or protein complexes made of 
threads of keratin, as well as with lipids. In the case of the 
corneocytes, the surfactants bind to these proteins allowing 
them to swell and making it possible for other ingredients 
in the formulation to penetrate into the lower layers of the 
skin where they can cause itching and irritation. The irrita¬ 
tion properties of surfactants have been demonstrated to be 
related to the mechanisms by which surfactants interact 
with the stratum corneum [11]. 

As for lipids, the interaction of surfactants with lipids in 
the stratum corneum is still not fully understood. Surfactants 
may get between the lipid bilayers causing increased perme¬ 
ability and even disruption of the bilayer [12]. Surfactants 
can also cause damage to the lipid structures themselves. 
Surfactants reduce the amount of lipids in the skin and 
disrupt skin barrier function by removing these lipids as the 
cleanser is used. It is not always the surfactants themselves 
that result in irritation, but other ingredients contained in 
the formulations (e.g. fragrances and preservatives). The 
surfactant effect on barrier function opens a pathway for the 
damaging effects of other ingredients. Obviously, compro¬ 
mising the skin barrier is best avoided as a compromised 
barrier has been correlated with skin disease including, pso¬ 
riasis, atopic dermatitis, and other ichthyoses [13]. 


Conclusions 

In conclusion, the advantages of non-foaming and low- 
foaming cleansers are mildness. The disadvantages are 


related to little foaming capability, but this should not be 
perceived by the consumer as representing ineffective 
cleansing. Cleansers that leave a "squeaky clean" feel to the 
skin surface and produce abundant foam may not be the 
best choice in patients with sensitive skin needs. Non¬ 
foaming and low-foaming cleansers achieve a delicate 
balance between skin cleansing and tolerability. 

References 

1 Draelos ZD. (2005) Concepts in skin care maintenance. Cutis 76 
(6 Suppl), 19-25. 

2 Effendy I, Maibach HI. (1994) Surfactants and experienmental 
irritant contact dermatitis. Contact Dermatitis 33, 217. 

3 Coria Laboratories, LTD. Products. Available from: URL:http:// 
www.cerave.com/mve.htm. Accessed September 2, 2008. 

4 Ananthapadmanabhan KP, Moore DJ, Subramanyan K, Misra 
M, Meyer F. (2004) Cleansing without compromise: the impact 
of cleansers on the skin barrier and the technology of mild 
cleansing. Dermatol Ther 17 (Suppl 1), 16-25. 

5 Kuehl BL, Fyfe KS, Shear NH. (2003) Cutaneous cleansers. Skin 
Therapy Lett 8 , 1-4. 

6 Agner T, Johansen JD, Overgaard L, Volund A, Basketter D, 
Menne T. (2002) Combined effects of irritants and allergens: 
synergistic effects of nickel and sodium lauryl sulphate in nickel- 
sensitized individuals. Contact Dermatitis 47, 21-6. 

7 Pedersen LK, Haslund P, Johansen JD, Held E, Volund A, Agner 
T. (2004) Influence of a detergent on skin response to methyldi- 
bromoglutaronitrile in sensitized individuals. Contact Dermatitis 
50, 1-5. 

8 Loffler H, Happle R. (2003) Profile of irritant patch testing with 
detergents: sodium lauryl sulfate, sodium laureth sulfate, and 
alkyl polyglucoside. Contact Dermatitis 48, 26-32. 

9 Slotosch CM, Kampf G, Loffler H. (2007) Effects of disinfectants 
and detergents on skin irritation. Contact Dermatitis 57, 235-41. 

10 Dykes P. (1998) Surfactants and the skin. Int J Cosmet Sci 20, 
53-61. 

11 Wilhelm ICP, Cua BC, Wolff HW, Maibach HI. (1993) Surfactant- 
induced stratum corneum hydration in vivo : prediction of the 
irritation potential of anionic surfactants. J Invest Dermatol 101, 
310-5. 

12 Walters KA, Bialik W, Brain KR. (1993) The effects of surfactants 
on penetration across the skin. Int J Cosmet Sci 15, 260-70. 

13 Marstein S, Jellum E, Eldjarn L. (1973) The concentration of 
pyroglutamic acid (2-pyrrolidone-5-carboxylic acid) in normal 
and psoriatic epidermis, determined on a microgram scale by gas 
chromatography. Clin Chim Acta 49, 389-95. 


105 




Chapter 14: Liquid hand cleansers and sanitizers 

Duane Charbonneau 

Procter & Gamble Co., Health Sciences Institute, Mason, OH, USA 


BASIC CONCEPTS 

• The hands are a common site for microbial contamination. 

• Hand cleansers and sanitizers are designed to reduce transient microbes on the skin surface with the intent of reducing the 
spread of infectious disease. 

• Hand cleansing products include liquid soaps with antimicrobial agents, alcohol-based hand sanitizers as well as non-alcohol- 
based hand sanitizers. 

• Hand hygiene technologies have decreased nosocomial infections. 

• Hands with damaged skin harbor more transient organisms than hands with healthy skin. 


Introduction 

Hand washes and hand sanitizers are designed to reduce 
transient microbes on the skin with the intent of reducing 
the spread of infectious disease. This class of products 
includes liquid soaps; liquid soaps with antimicrobial agents, 
alcohol-based hand sanitizers as well as non-alcohol-based 
hand sanitizers. 

Over the past 20 years there has been an increasing 
concern regarding infectious disease within the community 
and hospital. In the USA, deaths from infectious disease are 
ranked sixth among all deaths according to statistics pub¬ 
lished by the Centers for Disease Control and Prevention. 
Nosocomial infections are one of the most frequent and 
severe complications of hospitalization. Nosocomial infec¬ 
tions are the fourth leading cause of death in Canada and 
account for approximately 100 000 deaths annually in the 
USA [1,2]. These statistics are extremely sobering in light of 
all the advances made in modern medicine today. 

Several mitigating factors are responsible for the rising 
numbers of infection rates within the community as well as 
the hospital setting. First, is the changing nature and ranges 
of pathogens to which individuals within the community 
and hospital are exposed. Pathogens such as rotavirus, 
Campylobacter , Legionella , SARS, Escherichia coli 0157 ( E . coli), 
and norovirus were not commonplace prior to 1980. 
Additionally, methicillin-resistant Staphylococcus aureus 
(MRSA) and Clostridium difficile were largely considered 
hospital problems. Today, community-acquired MRS A 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


(CA-MRSA), norovirus, and new more virulent strains of 
C. difficile (02) are circulating within the general populous. 

Second, there are cultural changes that have a role in this 
increased infection burden, such as reduced hospital stays, 
in home care for elderly, ease of travel, and a large popula¬ 
tion of immunocompromised individuals. 

Third is the diminished research aimed at the identifica¬ 
tion of new antibiotics. It is no longer economically feasible 
for pharmaceutical companies to develop and register novel 
antibiotic technologies. This situation is further exacerbated 
by the increasing development of antibiotic resistance among 
common pathogenic microorganisms. 

With all of these issues, the mechanisms of dealing with 
infectious disease for the future must fall on prevention 
strategies in place of treatment regimes. Because hand 
contact has a crucial role in the transmission of infectious 
agents, it is imperative that consumers and hospitals have 
effective hand hygiene technologies. 


Hand microbiota 

Microbes that inhabit the hand are generally divided into 
two categories: transient and resident flora (Figure 14.1). 
The transient flora is microbes that inadvertently become 
attached to the hands following touching of contaminated 
surfaces; for example, a raw food item, or, as in the case of 
healthcare workers, an infected wound or body fluid. Several 
studies have documented the potential of this transfer of 
transient flora from hands to other parts of the body within 
an individual or alternatively between individuals. The 
classic example is the work by Hendley and Gwaltney [3] 
which demonstrated the importance of hand-to-hand trans¬ 
mission of the common cold vims. 


106 







14. Liquid hand cleansers and sanitizers 



Figure 14.1 The common flora of the hand. Transient flora are those 
microorganisms that are picked up from the environment. Resident flora 
are the microorganisms that routinely inhabit the skin. 


Table 14.1 Constituents of the hand resident flora. 

Organism 

Acinetobacter baumannii 
Acinetobacter johnsonii 
Acinetobacter Iwoffi 
Corynebacterium spp. 

Enterobacter agglomerans 
Enterobacter cloacae 
Klebsiella pneumoniae 
Propionibacterium acnes 
Pseudomonas aeruginosa 
Staphylococcus aureus 
Staphylococcus epidermidis 
Staphylococcus warned 
Streptococcus mitis 
Streptococcus pyogenes 


The resident flora of the hand is defined as the complex 
community of microbes that consistently inhabit the hand 
and routinely are not washed off with non-medicated soaps. 
A summary of the bacteria that have been reported to be 
isolated as resident flora is presented in Table 14.1. 

Unfortunately, few studies have been undertaken to 
clearly define the role that these microbes have in health 
and disease. However, it is speculated that the resident skin 


microbes are as essential to the health of the skin as the gut 
microorganisms are to overall health of the individual [4]. 
The resident flora provides positive health benefits by inhibi¬ 
tion of pathogens, immune modulation, and improving the 
integrity of the skin barrier. 

Although the resident skin flora usually has an essential 
role in protecting the host, under certain circumstances the 
resident flora can be pathogenic itself. For example, 
Staphylococcus epidermidis , an important member of the resi¬ 
dent skin flora, is also a common pathogen associated with 
wound infections. Further, it is estimated that approximately 
32% of the population carries the common pathogen 
Staphylococcus aureus as a member of the skin resident flora 
[4]. 

It would appear that frequent exposure to certain tran¬ 
sient microbes may lead to them becoming established as a 
constituent of the resident flora. For example, studies have 
shown that nurses performing similar tasks within a hospital 
will have some similarities among their resident flora; while 
those assigned to different tasks will have different constitu¬ 
ents within their resident flora [3,6]. Furthermore, it has 
recently been shown that homemakers often carrier bacteria 
within their resident hand flora that are identical to those 
environmental isolates identified within the home [7]. 

In terms of hand hygiene, the majority of hand soaps as 
well as hand sanitizers are primarily targeted toward reduc¬ 
ing the level of transient bacteria and viruses on hands. 
Some products provide only immediate activity (e.g. alcohol 
hand sanitizers), whereas others provide immediate and 
residual protection benefits (e.g. triclosan-containing hand 
sanitizers). Residual protection provides benefits in between 
product usage preventing re-establishment of transient 
flora. 


Hand hygiene 

Since the mid 1800s with the ground breaking work by 
Professor Ignaz Semmelweis demonstrating a reduction in 
puerperal sepsis following the institution of hand hygiene 
protocols, the concept of hand hygiene as means of infection 
control has been well accepted. In the late 1970s-1980s our 
understanding that the part hands play in the transmission 
of bacterial and viral pathogens including the common cold 
have become well documented [8,9]. Today, hand washing 
using soap and water or hand antisepsis using hand sanitizer 
products is the cornerstone of many infection control 
programs. 

Hand washing and hand antisepsis guidelines were pub¬ 
lished by the Association for Professionals in Infection 
Control (APIC) in 1988 and updated in 1993 [10]. The most 
recent updates were published in 2002 by the Hygiene Task 
Force composed of members of APIC, Center(s) for Disease 
Control (CDC), Healthcare Infection Control practices 


107 







HYGIENE PRODUCTS Cleansers 


Advisory Committee (HICPAC), Society for Healthcare 
Epidemiology of America (SHEA), and Infectious Diseases 
Society of America (IDSA) [11]. Since 1995 these various 
guidelines recognize the utility of hand washing with anti¬ 
microbial containing soap as well as the use of waterless 
hand sanitizers. The Food and Drug Administration's (FDA) 
Food Code contains specific hand hygiene guidance for retail 
and food service workers describing when, where, and how 
to wash and sanitize hands. Hand sanitizers, meeting specific 
criteria described in section 2-301.16 of the Food Code, may 
be used after proper hand washing in retail and food service 
[ 12 ]. 


Hand hygiene compliance 

The importance of hand washing is well understood by pro¬ 
fessional and non-professionals; unfortunately, observa¬ 
tional studies that measure compliance based on these 
standards are, at best, disappointing. Hand hygiene compli¬ 
ance studies estimate that healthcare workers are 40% com¬ 
pliant and food service workers are 30% compliant with 
standard guidelines [13,14]. A recent observational study 
demonstrated that fewer than 50% of hospital healthcare 
workers were observed to wash their hands after toileting 
[15]. Within the general population, observational studies 
have clearly demonstrated a gender difference among hand 
washing compliance. A large American Society for 
Microbiology study demonstrated that 88% of women and 
only 66% of men wash their hands after visiting the toilet. 
Other studies have shown that hand washing compliance is 
inversely proportional to education levels, indicating that 
the understanding of guidelines is not the issue [16]. Because 
hand washing compliance is low there is a need for hand 
sanitizers, especially those with persistent benefit, to be 
included in hand hygiene strategies. 


Hand washing techniques 

Hand washing when done properly is considered to be the 
gold standard for removing transient pathogenic bacteria 
from the hands. The best accepted hand washing protocol 
established by the CDC is described below. 

Proper hand washing with soap and water 

• Wet your hands with warm, running water and apply 
liquid soap or use clean bar soap. Lather well. Rub your 
hands vigorously together for at least 15-20 seconds. 

• Scrub all surfaces, including the backs of your hands, 
wrists, between your fingers and under your fingernails. 

• Rinse well. 

• Dry your hands with a clean or disposable towel. 

• Use a towel to turn off the faucet. 


The most effective mean wash time is considered to be 
15-20 seconds, but observational studies on subjects within 
healthcare and community settings indicate that the average 
hand wash time lasts less than 8 seconds. This would imply 
that as currently practiced the removal of transient micro¬ 
organisms from the hands is suspect at best. Quantitative 
studies within a community setting have substantiated this 
hypothesis. A study conducted by Larson et al. [17] in home¬ 
makers measured mean colony-forming units count of 5.72 
before washing and 5.69 after. These results indicated that 
the hand washing technique as practiced was ineffective. 

A final factor for consideration is that of pH. The low pH 
of the hands has a crucial role in the innate antimicrobial 
hostility of the hand surface. The pH of the hands is approxi¬ 
mately 4-5 routinely; however, the alkalinity of soaps can 
result in an increase in the skin pH [18]. This poses a concern 
because some of the antibacterial characteristics of skin are 
minimized. In one report, pH increased 0.6 to 1.8 units after 
hand washing with plain soap and then gradually declined 
to baseline levels over a period of 45 minutes to 2 hours 
[18]. Recently, a hand sanitizer has been introduced that 
provides antibacterial efficacy using triclosan formulated 
into a low pH matrix. This product maintains the low pH of 
the hand surface for hours. This imparts not only an imme¬ 
diate antimicrobial benefit but a persistent one as well [19]. 

Several studies have demonstrated that damaged hands 
harbor more transient microorganisms than healthy hands 
[20]. Repeated hand washing with soap and water removes 
the protective lipid layer which is followed by transepider- 
mal water loss and cutaneous signs of redness, scaling, and 
possibly dermatitis. The use of alcohol-based hand sanitizers 
can also lead to dehydration of the skin as well as lipid 
removal and skin damage which may lead to increased colo¬ 
nization by transient flora. Recent investigations have shown 
that only subjects with healthy skin achieved appropriate 
levels of decontamination with plain soap and water [20]. 
Thus, individuals with damaged hands will require more 
robust antimicrobial formulations. 


Measurements of efficacy 

Studies demonstrating the efficacy of antimicrobial hand 
soaps and sanitizers toward removal of transient microbes 
can be divided into three categories: 

1 In vitro potency and spectrum of activity; 

2 In vivo models with artificial inoculate; and 

3 Clinical studies demonstrating efficacy. 

In vitro measurements 

In terms of the in vitro measures of efficacy, classic micro- 
biologic protocols of minimum inhibitory concentration 
(MIC) and time kill studies are usually conducted with bac¬ 
teria and viruses of interest. The relevance of these in vitro 


108 





14. Liquid hand cleansers and sanitizers 


measurements for products of this nature has been a debate 
within the research community for decades. The primary 
information garnered from these studies only provides 
insights into the potency and spectrum of activity of a for¬ 
mulation within the test laboratory setting. 

Investigators have also relied on artificial substrates to 
model removal of transient flora from hands. In these model 
systems either pig skin or an alternative skin substrate mimic 
is utilized to model the hand. Bacteria or viruses are inocu¬ 
lated onto the substrate prior to treatment. Measurements 
of microbial reductions are made following the treatment 
and efficacy is calculated by comparison with either an 
untreated control or placebo. Recently, some researchers are 
using similar models to assess the residual benefits of these 
formulations. The waterless alcohol-based hand sanitizer 
technologies have little to no residual benefit versus the 
triclosan-containing low pH hand sanitizers which provide 
immediate as well as residual benefit (2008 Nonprescription 
Medicines Academy). 

In vivo models with artificial inoculate mimic 
transient flora 

Both in Europe and the USA, there are efficacy standards 
for antimicrobial soaps and hand sanitizers. In both geo¬ 
graphic regions, the tests necessary to fulfill these regulatory 
requirements involve artificially inoculating subject's hands 
with large inoculums of indicator bacteria. This is followed 
by treatment, neutralization of the active ingredient, and 
enumeration of remaining viable bacteria. 

The methods most widely accepted in Europe are EN 1499 
for antimicrobial hand soaps and EN 1500 for leave-on hand 
sanitizers. In both of these test protocols, 12-15 subjects 
wash their hands with a plain soap and water. The hands 
are then contaminated by having the subject immerse their 
hands half-way to metacarpals in a 24-hour broth culture 
of a non-pathogenic strain of E. coli. Following drying, bacte¬ 
rial recovery is achieved by kneading the fingertips and 
palms separately into lOmL Trypticase soy broth plus neu¬ 
tralizers. The hands are removed, disinfected, and again 
contaminated. The treatments are then applied for 30-60 
seconds either with or without a rinsing step depending on 
product type (rinse-off or leave-on). Post-treatment bacteria 
are recovered as described above. Extracted bacteria are 
enumerated using traditional microbiologic plating tech¬ 
niques. In these European tests, efficacy is determined 
versus internal standards. For EN 1499, antimicrobial hand 
soaps must provide a superior log reduction to that achieved 
using a plain soap (sapo kalinus) following a 60-second 
treatment. When evaluating leave-on products such as hand 
sanitizers with EN 1500 procedures, the product must 
deliver a benefit not less than that observed with a 60- 
second application of 60% 2-propanol. 

In the USA, antimicrobial soaps and sanitizers are regu¬ 
lated by the FDA's Tentative Final Monograph for Healthcare 


Antiseptic Drug Products (FR 1994). The standard method 
used to evaluate formulations is the American Society of 
Testing and Materials E 1174. In this test, subjects refrain 
from utilizing any antimicrobial products for 1 week prior 
to the start of the study ("washout period"). At the initiation 
of the study, the subjects perform a cleansing wash to elimi¬ 
nate any residual transient bacteria. The subjects' hands are 
then contaminated with 4.5-5.0mL of a 24-hour broth 
culture of either a non-pathogenic E. coli or Serratia marces- 
cens. Bacteria are then recovered by separately placing each 
hand into a glove containing 7 5 mL sampling solution plus 
neutralizers. The hand is massaged for 1 minute and bacteria 
are enumerated using traditional microbiologic plating tech¬ 
niques. This enumeration serves as the baseline measure¬ 
ment. The subjects then perform another cleansing wash 
and are reinoculated. Following this reinoculation the treat¬ 
ment is applied as described by the manufacture for either 
an antimicrobial soap or leave-on hand sanitizer. After the 
treatment is completed the bacteria are again recovered from 
the hands using the glove method and this is called Test 
Wash 1. This is followed by another cleansing wash. Once 
this cleansing wash is complete a cycle of inoculation fol¬ 
lowed by treatment is performed 10 consecutive times and 
bacteria are recovered at the 10th cycle. In this protocol, 
there is no internal standard. The success criteria are deter¬ 
mined by log reduction versus the baseline measurement. 
In Wash 1, a product must achieve a minimum of a 2-log 
reduction, and at Wash 10, the product must deliver a 3-log 
reduction versus baseline. 

Methodology concerns 

There is a great deal of critique of these standard methods. 
First and foremost, these European and US protocols utilize 
treatment times and typically volumes of product that are 
far outside of the norm. In the case of the ASTM El 174, 
there is concern that bacteria are sampled from areas of the 
hands not involved in transmission such as the back of the 
hands. An additional concern is the appropriateness of these 
inocula to the real world situation. In the natural setting, 
transient bacteria would rarely be present without being 
incorporated into a soil matrix. 

To address this issue, investigators have developed meth¬ 
odologies that incorporate the use of a soil matrix such as 
chicken or hamburger in place of marker bacterial organisms 
and focused attention is paid to the palms of the hands 
[21,22]. In the presence of a greasy soil matrix such as 
chicken, the alcohol-based hand sanitizers lack appreciable 
efficacy, whereas those containing more potent antimicro¬ 
bial actives such as triclosan and benzalkonium chloride 
demonstrate a higher level of effectiveness (Figure 14.2). 

In addition to these standardized methodologies, other 
protocols designed to mimic transient flora have been pre¬ 
sented within the literature. The most utilized method is 
commonly referred to as the fingerpad method [23]. In this 


109 


HYGIENE PRODUCTS Cleansers 




(a) (b) (c) 

Figure 14.2 Effects of different hand sanitizers on greasy soil. Bacterial growth has been colorized, (a) Untreated, (b) Triclosan-based. (c) Alcohol-based. 



method, subjects who have previously refrained from using 
antimicrobial products have their fingerpads contaminated 
with either bacteria or viruses. The fingerpads are then 
treated with test product and the bacteria or viruses are 
enumerated. Recently, authors have utilized this test to 
evaluate the residual activity of a hand sanitizer. In this test 
the fingerpad was treated with the sanitizer and subse¬ 
quently challenged with bacteria 3 hours later [19]. This 
study demonstrated that the hand sanitizer provided protec¬ 
tion from microbial challenge for up to 3 hours post applica¬ 
tion. Other models have also been described in the literature 
with the aim of assessing residual antimicrobial activity as 
well as transfer of microbial agents. One such method 
involves the ability of antiseptic hand products to interrupt 
the transfer of microorganisms from fingerpads to hard sur¬ 
faces under controlled pressures [24]. 

Resident flora 

For consumer or common healthcare, antimicrobial hand 
soaps and hand sanitizers various methods have been devel¬ 
oped to look at the impact of these products on the resident 
flora. One commonly used method is the Cade test which 
measures the impact of several washes over a period of 3 
days [23]. This test, like the Health Care Personnel Handwash 
test, begins with a washout period. This is followed by a 
5-day baseline period and samples are collected over 2 days 
to control for day-to-day variations. Following this baseline, 
subjects are instructed to use the product multiple times 
daily. Subjects are sampled for 2 days during the treatment 
phase. Efficacy is determined by comparisons between the 
baseline and treatment phases. 

The antimicrobial efficacy of surgical hand antiseptics is 
determined according to a European standard (prEN 12791) 
and a US standard (TFM). The two methods differ in several 
ways as shown in Table 14.2. 

Because of these differences, Kampf et al. [26] have 
stressed the need to evaluate potential products using both 


Table 14.2 US and European standard methods. 


Difference 

US method 

prEN 12791 

Product application 

Hands and lower 

forearm 

Hands only 

Number of applications 

11 over 5 days 

Single application 

Sampling times 

0, 3, 6 hours 
post-application 

0, 3 hours 
post-application 

Sample method 

Glove juice 

Fingertip sampling 

Success criteria 

Absolute bacterial 

reduction 

Non-inferiority to 
reference standard 


methodologies to assure efficacy. Overall, the model systems 
described above have been very helpful for the determina¬ 
tion of efficacy for various antimicrobial hand soaps and 
hand sanitizers. However, it must be pointed out that these 
models are not always indicative of efficacy under real use 
conditions. 


Effectiveness of hand hygiene in the 
community setting 

Unfortunately, clinical trials of hand hygiene regimes are 
complex and expensive to execute. Community interven¬ 
tion studies have been limited in scope and have delivered 
mixed and sometimes inconclusive results. Comprehensive 
reviews of these studies have resulted in less than favorable 
outcomes in terms of the quality and the conclusions derived 
[27]. Reduction in gastrointestinal illnesses associated with 
handwashing have ranged from -10 % to 5 7 %. Unfortunately, 
only three out of the five studies that evaluated gastrointes¬ 
tinal illness produced statistical significance. In these three 


110 










14. Liquid hand cleansers and sanitizers 


studies, the magnitude of the impact was approximately 
50% reduction in the incidence of illness. The impact of 
hand hygiene on respiratory illness is more limited. The 
magnitude of the overall impact of current available studies 
has been estimated to be an approximate 23% reduction in 
the incidence rate of respiratory infections. Thus, current 
data implies that hand hygiene has its largest impact on 
gastrointestinal versus respiratory illness. A recent meta¬ 
analysis by Aiello et al. [28], using hand hygiene interven¬ 
tion studies, indicated that overall hand hygiene reduces the 
incidences of gastrointestinal illness by 31% (95% Cl = 19- 
42%) and, to a lesser extent, respiratory illness by 21% 
(95% Cl = 5-34%). 

There are many more studies that examined the impact 
of alcohol-based hand sanitizers on subsequent infection 
rates. The conclusion by Meadows and LeSaux [29] was that 
the data were of poor quality and that more rigorous inter¬ 
vention studies were needed. The current studies have dem¬ 
onstrated a reduction in the incidence of gastrointestinal 
illness from 0 to 59%. The magnitude for respiratory illness 
and infection and/or symptom reduction ranged from -6% 
to 26%. Thus, like the hand washing studies, the use of 
alcohol-based hand sanitizers appears to have a more robust 
effect on gastrointestinal infections. 


Hospital epidemiology noscomial studies 

To date, several reviews have examined the database of 
studies evaluating the evidence of a causal link between 
hand hygiene and the reduced risk of hospital acquired 
infections. A recent comprehensive review by Backman 
et al. [30] evaluated 1120 articles on the subject and con¬ 
cluded that "there is a lack of rigorous evidence linking 
specific hand hygiene interventions with the prevention of 
health care acquired infections." The conclusion from the 
Backman review was somewhat different from that of 
Larson's review [31] but was similar to Silvestri etal/s review 
[32] concerning the link between hand hygiene interven¬ 
tions and the risk of healthcare acquired infections. However, 
it is important to note that all three reviews focused on the 
lack of quality in studies published to date. It is speculated 
that the nature of the interventions utilized and the diverse 
factors affecting the acquisition of healthcare-associated 
infections that complicate the ability to demonstrate an 
effect of hand hygiene alone. 


Safety of handwashes and hand sanitizers 

Irritation associated with handwashes and 
hand sanitizers 

A safety concern for both hand washes and hand sanitizers 
is the occurrence of dermatitis observed in up to 25% of 


healthcare workers [33]. It is most often attributed to irrita¬ 
tion which occurs from repeated contact with detergents 
and is believed to be exacerbated by the wearing of gloves. 
A further concern has to do with contact allergies to anti¬ 
bacterial actives and perfumes that are incorporated within 
the products themselves. Although there are some reports 
of allergies to these chemistries the accounts of these are 
limited within the literature [34]. 

Safety concerns specific to alcohol-based 
hand sanitizers 

In terms of the alcohol-based hand sanitizers, there are 
occupational safety concerns with the chronic use of alcohol. 
First is the removal of the lipid barrier of the hands, leading 
to irritation and an increase in bacterial colonization. 
Second, the flammability of these alcohol-based formula¬ 
tions has caused some to question whether it is good prac¬ 
tice to have them in various locations where the potential 
for ignition exists. Third are the reports in the literature of 
intentional ingestion of the alcohol-based products by those 
individuals with alcoholism and the accidental ingestion by 
children [35]. Lastly, a safety issue that has called alcohol- 
based systems into question is the misuse of these products 
for the prevention of infections. For example, use of alco¬ 
hol-based hand sanitizers for prevention of infections by 
norovirus or C. difficile is not prudent because it is well 
established that alcohol has limited efficacy against these 
pathogens [36,37]. 

Microbial resistance to antimicrobial agents 

The major question concerning antimicrobial-containing 
hand washes and their use in consumer products has to do 
with the potential for the development of pathogen resist¬ 
ance [38]. The resistance issue has been divided into two 
questions: 

1 Will the use of these agents in broad scale consumer use 
result in the loss of their effectiveness? 

2 Will the use of these agents lead to cross-resistance to 
antibiotics? 

The majority of the work has been done with triclosan, 
which has been utilized as an antibacterial agent in several 
consumer products for 30 years. Triclosan is broad-spectrum 
antibacterial and antifungal agent. It is more potent against 
Gram-positive (e.g. S. aureus) than Gram-negative bacteria. 
Triclosan is utilized for therapeutic baths of MRSA-infected 
patients [39] and in the control of MRS A carriage and skin 
infections [40]. Unlike orally ingested antibiotics, triclosan 
elicits bactericidal actions against a variety of bacterial targets 
reducing the potential for resistance development. 

Laboratory observations 

Chronic sublethal exposure of laboratory strains of E. coli to 
triclosan selected clones with reduced susceptibility [41]. 


Ill 




HYGIENE PRODUCTS Cleansers 


Although these clones were less susceptible, they were still 
inhibited by in-use triclosan concentrations. Further studies 
demonstrated that these observations were limited only to 
laboratory strains of E. coli and in some cases the effects 
observed with triclosan could be reproduced with a variety 
of non-antimicrobial materials such as mustard, chili, and 
garlic [42,43]. 

Lambert [44] evaluated 236 clinical isolates of P. aeruginosa 
and S. aureus over a 10-year period. There was no difference 
in triclosan sensitivity between antibiotic sensitive and 
resistant strains. The authors concluded that there was a 
negative correlation between antibiotics and biocides. Sutler 
and Russell [45] used clinical isolates of S. aureus (MSSA and 
MRSA) to demonstrate no correlation between MRSA and 
decreased triclosan susceptibility. Furthermore, continuous 
exposure of a triclosan-sensitive S. aureus strain to subinhibi- 
tory triclosan concentrations for 1 month did not decrease 
susceptibility either to triclosan or to other antibiotics. 

Antibacterial exposure results from 
long-term studies 

Studies examining exposure to triclosan for 6 months of 
mixed microbial communities derived from natural environ¬ 
ments [46] resulted in no change in triclosan or antibiotic 
sensitivities. 

Cole et al. [47] studied 60 homes, 30 of which used anti¬ 
bacterial products and 30 did not. A total of 1238 bacteria 
were evaluated, with more target bacteria being recovered 
from biocide users versus non-users. No methicillin, oxacil¬ 
lin, or vancomycin resistant S. aureus were isolated associ¬ 
ated with the use of biocides. In fact, the incidence of 
resistance to antibacterials was higher in non-user house¬ 
holds. Aiello et al. [48] conducted a large (224 households), 
12-month study addressing the impact of antibacterial prod¬ 
ucts in homes. Logistic regression analysis demonstrated that 
the use of biocide products did not result in significant 
increases in antimicrobial drug resistance nor did it impact 
susceptibility to triclosan. 

Thus, following a comprehensive review of the scientific 
literature, it is concluded that there is no evidence to support 
that use of triclosan in consumer products will reduce effec¬ 
tiveness nor contribute to the societal burden of antibiotic 
resistance. In fact, several accounts in the literature docu¬ 
ment the utility of triclosan in the reduction of antibiotic- 
resistant microorganisms including MRSA. 


Formulations of hand sanitizers and 
hand washes 

Hand sanitizers can be categorized into three main classes: 

1 Alcohol-based = >62% alcohol; 

2 Alcohol-based supplemented = >62% alcohol plus antimi¬ 
crobial agent; 


3 Non-alcohol-based = the majority of the product is water 
plus surfactant and antimicrobial agent. 

In terms of product forms, they span from liquids to gels 
and foams. Most base efficacy on the fact that they are leave- 
on products. With the exception of the alcohol-based prod¬ 
ucts that only deliver an immediate benefit and provide no 
residual activity, hand sanitizers provide both immediate 
plus a residual antimicrobial benefit. 

The antimicrobial hand washes are primarily water-based 
formulations that are composed of mixtures of surfactants, 
antimicrobial actives perfumes, and, in some cases, emol¬ 
lients. In many cases, these emollients and skin feel agents 
are added to improve the consumer experience with the 
hope of improving the overall compliance. In the USA, anti¬ 
microbial actives that can be incorporated within these prod¬ 
ucts are regulated under the TFM. The ingredients are 
classified into three categories: 

1 Category 1. Ingredients determined to be safe and 
effective; 

2 Category 2. Ingredients determined to be neither safe nor 
effective; 

3 Category 3. Ingredients for which there is insufficient evi¬ 
dence; however, the FDA is not objecting to marketing or 
sale of these products. 

Only active ingredients in categories 1 and 3 are allowed 
to be lawfully marketed in products within the USA. 

The formulating of non-alcohol-based hand sanitizers as 
well as antimicrobial hand washes must take into considera¬ 
tion the bioavailability of the antimicrobial active. For 
example, some of the surfactants within the formulation 
may complex or otherwise inactivate the formulation. 
Recent data with triclosan-containing formulations have 
demonstrated a difference in efficacy among various 
triclosan-containing hand washes [49] with varying 
formulations. 


Future directions 

It is imperative for our future understanding of this area that 
improved epidemiologic studies be conducted with a variety 
of hand hygiene products to better demonstrate the role of 
hand hygiene for the prevention of infections both in the 
hospital as well as in the community setting. Additionally, 
complete hand hygiene strategies must be developed includ¬ 
ing product efficacy, skin feel, compliance, as well as educa¬ 
tion. Furthermore, hand hygiene must be examined to 
assure consumers that both residual as well as immediate 
germ removal is accomplished. Technologies need to be 
developed that address consumer as well as healthcare 
workers' behavior and occupational needs. These technolo¬ 
gies must be easy to use and provide the skin conditioning 
needs for consumers and be effective against a variety of 
pathogenic bacteria and viruses. 


112 




14. Liquid hand cleansers and sanitizers 


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17 Larson EL, Gomez-Duarte C, Lee LV, Della-Latta P, Kain DJ, 
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19 Zukowski C, Boyer A, Andrews S, Trowbridge M, Grender J, 
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21 Charbonneau DL, Ponte JM, Kochanowski BA. (2000) A method 
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22 Hansen TB, Knochel S. (2003) Image analysis method for evalu¬ 
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23 Sattar SA, Ansari SA. (2002) The fingerpad protocol to assess 
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24 Mbithi JN, Springthorpe VS, Boulet JR, Sattar SA. (1992) 
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26 Kampf G, Ostermeyer C, Heeg P, Paulson D. (2006) Evaluation 
of two methods of determining the efficacies of two alcohol- 
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27 Bloomfield SF, Aiello AE, Cookson B, O'Boyle C, Larson EL. 
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29 Meadows E, Le Saux N. (2004) A systematic review of the effec¬ 
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tion of illness-related absenteeism in elementary school children. 
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32 Silvestri L, Petros AJ, Sarginson RE, de la Cal MA, Murray AE, 
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33 Larson E, Friedman C, Cohran J, Treston-Aurand J, Green S. 
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34 Heydorn S, Menne T, Johansen JD. (2003) Fragrance allergy and 
hand eczema: a review. Contact Dermatitis 48, 59-66. 

35 Emadi A, Coberly L. (2007) Intoxication of a hospitalized patient 
with an isopropanol-based hand sanitizer. N Engl J Med 356, 
530-1. 

36 Macinga DR, Sattar SA, Jaykus LA, Arbogast JW. (2008) 
Improved inactivation of nonenveloped enteric viruses and their 
surrogates by a novel alcohol-based hand sanitizer. Appl Environ 
Microbiol 74, 5047-52. 

37 King S. (2004) Provision of alcohol hand mb at the hospital 
bedside: a case study. J Hosp Infect 56 (Suppl. 2), S10-2. 

38 Aiello AE, Larson E. (2003) Antibacterial cleaning and hygiene 
products as an emerging risk factor for antibiotic resistance in 
the community. Lancet Infect Dis 3, 501-6. 

39 Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA. 
(1995) Use of 0.3% triclosan (Bacti-Stat) to eradicate an out¬ 
break of methicillin-resistant Staphylococcus aureus in a neonatal 
nursery. Am J Infect Control 23, 200-8. 

40 Rashid A, Solomon LK, Lewis HG, Khan K. (2006) Outbreak of 
epidemic methicillin-resistant Staphylococcus aureus in a regional 
burns unit: management and implications. Burns 32, 452-7. 

41 Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, 
Slabas AR, et al. (1999) Molecular basis of triclosan activity. 
Nature 398, 383-4. 

42 Rickard AH, Lindsay S, Lockwood GB, Gilbert P. (2004) Induction 
of the mar operon by miscellaneous groceries. J Appl Microbiol 
97, 1063-8. 


43 McBain AJ, Ledder RG, Sreenivasan P, Gilbert P. (2004) Selection 
for high-level resistance by chronic triclosan exposure is not 
universal. J Antimicrob Chemother 53, 772-7. 

44 Lambert RJ. (2004) Comparative analysis of antibiotic and 
antimicrobial biocide susceptibility data in clinical isolates of 
methicillin-sensitive Staphylococcus aureus , methicillin-resistant 
Staphylococcus aureus and Pseudomonas aeruginosa between 1989 
and 2000. J Appl Microbiol 97, 699-711. 

45 Suller MT, Russell AD. (2000) Triclosan and antibiotic resistance 
in Staphylococcus aureus. J Antimicrob Chemother 46, 11-8. 

46 McBain AJ, Bartolo RG, Catrenich CE, Charbonneau D, Ledder 
RG, Price BB, et al. (2003) Exposure of sink drain microcosms 
to triclosan: population dynamics and antimicrobial susceptibil¬ 
ity. Appl Environ Microbiol 69, 5433-42. 

47 Cole EC, Addison RM, Rubino JR, Leese KE, Dulaney PD, 
Newell MS, et al. (2003) Investigation of antibiotic and antibac¬ 
terial agent cross-resistance in target bacteria from homes of 
antibacterial product users and nonusers. J Appl Microbiol 95, 
664-76. 

48 Aiello AE, Marshall B, Levy SB, Della-Latta P, Lin SX, Larson E. 
(2005) Antibacterial cleaning products and drug resistance. 
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putida. Am J Infect Control 32, E22. 


114 


Chapter 15: Shampoos for normal scalp hygiene 
and dandruff 


James R. Schwartz, Marcela Valenzuela, and Sanjeev Midha 

Procter & Gamble Beauty Science, Cincinnati, OH, USA 


BASIC CONCEPTS 

• Frequent scalp cleansing is important to prevent formation of unhealthy scalp. 

• Three classes of shampoos can be delineated: (1) cosmetic shampoos and two types of therapeutic products, (2) standard, and 
(3) cosmetically optimized therapeutics. 

• Both therapeutic scalp care shampoos are effective for normal scalp to prevent unhealthy conditions and for dandruff/seborrheic 
dermatitis scalp to treat the condition and subsequently prevent its reoccurrence. 

• All therapeutic shampoos are not equally efficacious, even though they may contain the same active. 

• Cosmetically optimized therapeutic shampoos are desirable as they increase compliance long term because of having no esthetic 
trade-offs and their affordability. 

• All shampoos, including cosmetics, must be mild to the skin while being effective cleansers to minimize irritation that could 
initiate scalp problems. 


Introduction 

The scalp is a unique environment of the skin combining a 
high level of sebaceous lipid production with a physical 
covering of hair. The hair physically protects the scalp from 
UV light but also can inhibit the cleansing efficiency of the 
scalp surface by shampoos. These conditions allow for the 
colonization of commensal Malassezia yeasts which can, 
under the right conditions, cause inflammation and hyper¬ 
proliferation [1] leading to symptoms [2] of flakes and itch 
(Figure 15.1). Lipases are secreted by the yeast into the sur¬ 
rounding medium to cause liberation of fatty acids from the 
triglycerides of the sebaceous lipids. Malassezia selectively 
consume long chain saturated fatty acids to live, the unsatu¬ 
rated fatty acids left behind can then be the initiators of 
inflammation. Cutaneous inflammation results in hyperpro¬ 
liferation in the epidermis leading to immature stratum 
corneum cells with incompletely degraded adhesive func¬ 
tion resulting in removal as visible clumps. 

The resultant condition is called dandruff or seborrheic 
dermatitis (D/SD), depending on the severity of flaking and 
the presence of outward manifestations of inflammation. 
The presence of the condition places special requirements 
on effective scalp cleansing and it has been observed that 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


scalp issues such as D/SD occur more frequently when 
cleansing frequency decreases [3]. Because the sebaceous 
lipids are one of the key factors required for formation of 
D/SD, infrequent removal leads to the build up of the pro- 
inflammatory by-products of Malassezia metabolism. 


Product and formulation 
technology overview 

Three categories of shampoos can be delineated (Figure 
15.2). Cosmetic shampoos are primarily designed to cleanse 
the hair, but of course the scalp skin is cleansed simultane¬ 
ously. Modern versions of these shampoos also condition the 
hair by depositing certain ingredients on the hair to improve 
cosmetic benefits such as ease of combing, shine mainte¬ 
nance, and other attributes important to all consumers. 
Therapeutic scalp care shampoos (often termed "antidan¬ 
druff") contain active ingredients to control the D/SD condi¬ 
tions, most often by reducing the Malassezia population on 
the scalp. Standard therapeutic products tend to focus on 
the drug active without full consideration of product esthet¬ 
ics. Cosmetically optimized therapeutic products also contain 
a drug active to achieve therapeutic benefits, but without 
the common esthetic trade-offs of therapeutic products. 
Recommendations involving therapeutic products must take 
into consideration that patients also have basic hair care 
needs and that if the product has significant negative esthetic 
trade-offs, compliance will be very poor thereby limiting 
therapeutic efficacy. 


115 








HYGIENE PRODUCTS Cleansers 





(a) (b) (c) 

Figure 15.1 (a) Image of normal scalp skin, (b) Dandruff scalp image showing adherent white flakes, (c) Seborrheic dermatitis with more evidence of 
sebum yellowing on flakes and underlying erythema. 



Mild for everyday usage O 

Hair conditioning O 

Pleasant product esthetics O 

Cost effective O 

Anti-dandruff efficacy 


O 

O 

O 

O 

o o 


Figure 15.2 Representation of the shampoo segments, differentiating 
cosmetic from therapeutic shampoos and their key attributes. The 
category of cosmetically optimized therapeutics achieves therapeutic 
benefits without diminishing esthetic attributes. 


The primary component of all shampoos is surfactants 
which help to remove sebaceous lipids, keratin debris, par¬ 
ticulates from the air, and residues from styling products 
(Table 15.1). These materials are responsible for the lather¬ 
ing action of a product; the volume of lather is important in 
the user's perception of cleaning activity. Most of the sur¬ 
factants tend to be negatively charged (anionic), although 
some contain both positive and negative charges in the same 
molecule (amphoteric), and some are uncharged (non¬ 
ionic); these latter types are considered co-surfactants and 
function to optimize the lather quality and amount and 
cleaning ability of the primary anionic surfactant. 

The surfactant system is optimized to achieve two oppos¬ 
ing objectives - cleaning while minimizing irritation of the 
skin. All surfactants have the potential to irritate the skin to 
various degrees. The goal of the formulator is to achieve 


effective cleaning and lathering while minimizing the irrita¬ 
tion potential of the product by using the right surfactants. 
The addition of co-surfactants can synergistically decrease 
irritation potential without harming cleaning. Some anti¬ 
dandruff actives also can minimize the irritation potential of 
surfactants (see below); this is especially important for treat¬ 
ment of the D/SD condition which can be exacerbated by 
an irritating surfactant system. 

In addition to surfactants for cleaning, shampoos contain 
a wide range of other materials to care for the hair and scalp, 
deliver cosmetic benefits, enhance the usage experience, 
and to maintain the physical integrity of the product itself 
(e.g. preservatives, viscosity adjusters, pH control). Hair con¬ 
ditioning agents result in shiny, manageable hair and include 
such materials as silicones, cationic (positively charged) pol¬ 
ymers that show enhanced deposition on the hair fiber to 
reduce static electricity, humectants to maintain hydration, 
and materials that penetrate the hair shaft to maintain a 
healthy-looking appearance. 

The cationic polymers mentioned as conditioning aids are 
also a critical component of the delivery system of many 
shampoos. While shampoos are first and foremost designed 
to clean, the achievement of additional hair and scalp ben¬ 
efits requires selected materials to be left behind after rinsing 
to deliver these benefits. The combination of oppositely 
charged surfactants and polymers results in an electrostatic 
association complex called coacervate which forms upon 
product use and rinsing. The coacervate is an aqueous gel 
that aids in the delivery of hair and scalp benefit agents to 
their respective surfaces. 

The manipulation of surfactant and polymer types affects 
deposition efficiency, and together with the type and level 
of hair benefit agent(s), affects how much conditioning is 
delivered to the hair. This is the basis for a wide offering of 
shampoo versions, to meet the diverse hair and scalp needs 
of users to deliver cosmetic benefits and a pleasant in-use 
experience, especially in terms of how much hair condition¬ 
ing is needed and desired. Standard therapeutic shampoos 


116 





15. Shampoos 


Table 15.1 Summary of common formulation components of various shampoo types. 


Function(s) 


Material 

class(es) 

Common examples 

Presence in 






Cosmetic 

Cosmetically 

Standard 






shampoo 

optimized 

therapeutic 






therapeutic 

shampoo 

Lather/cleaning 


Primary 

Sodium lauryl sulfate, 

Yes 

Yes 

Yes 



surfactants 

ammonium lauryl sulfate, 
sodium laureth sulfate, 
ammonium laureth sulfate 





Optimization 

Co-surfactants 

Cocamidopropyl betaine, 

Yes 

Yes 

Yes 




Cocamide MEA 




Hair conditioning 

Shine, 

Silicones 

Dimethicone, dimethiconol, 

Yes 

Yes 


agents 

manageability 


amodimethicone 





Detangling, 

Cationic polymers 

Polyquaternium-10, cationic 

Yes 

Yes 



Antistatic 


guar derivatives 





Hydration 

Humectants 

Glycerin, urea 

Some 

Some 



Hair health 


Panthenol and derivatives 

Some 

Some 


Deposition aids 

Benefit delivery 

Cationic Polymers 

Polyquaternium-10, cationic 

Yes 

Yes 





guar derivatives 




Preservatives 


Biocides 

Isothiazalinone derivatives, 

Yes 

Yes 

Yes 




parabens 




Fragrance 




Yes 

Yes 

Yes 

Thickeners 

Viscosity 

Salts 

Sodium chloride 

Yes 

Yes 

Yes 



Particles 

Glycol distearate 

Some 

Some 

Some 

Antidandruff 

Scalp care 

Antifungals 

Pyrithione zinc (PTZ), 


Yes 

Yes 

components 



selenium sulfide, 
ketoconazole (Table 15.2) 






Potentiators 

Zinc carbonate 


Some 




tend to be deficient in hair conditioning benefits. They also 
do not tend to have a range of versions to meet the esthetic 
needs of the user. Together these two factors limit compli¬ 
ance with standard therapeutic products. 

Therapeutic scalp care shampoos additionally contain active 
materials for resolving D/SD and preventing its reoccurrence. 
Because the commensal scalp fungus Malassezia clearly has 
a role in the etiology of the condition [1], the primary 
function of most scalp care active materials is antifungal; 
the most common are referred to in Table 15.2, grouped 
by their intrinsic anti -Malassezia potency. Many of the 
materials are accepted by global regulatory agencies, while 
some are used in more limited geographic applications. 

The most commonly used scalp active is pyrithione zinc 
(PTZ), a material developed as part of a program to identify 
biocides based on the naturally occurring antibiotic aspergil- 
lic acid [4]. Screening of over 1000 prospective antidandruff 


materials in the late 1950s led to the selection of PTZ; novel 
formulation work then led to commercialization of sham¬ 
poos with PTZ in the early 1960s [5]. Since that time, the 
efficacy, ease of formulation, cost, and compatibility with 
esthetic shampoos has resulted in very broad use and accept¬ 
ance of PTZ and technical developments which continue to 
improve its therapeutic benefit (see below). 

Other effective actives such as ketoconazole and selenium 
sulfide are used fairly broadly, but tend to be more limited 
to the standard therapeutic class of shampoos either because 
of cost, regulatory, or esthetic limitations. Such products are 
generally used when especially difficult cases of D/SD occur. 
If such products are needed, subsequently switching to cos¬ 
metically optimized therapeutic shampoos should be advised 
for prophylactic usage. Materials such as climbazole and 
octopirox have been used regionally, but have been limited 
by the lack of acceptance by the US Food and Drug 


117 






HYGIENE PRODUCTS Cleansers 


Table 15.2 Overview of scalp care active materials. 


Common actives 

Primary 

mechanism 

Typical 

amount 

used 

Physical characteristics 

Usage 


Appearance 

Odor 


Most potent antifungal activity 





Pyrithione zinc (PTZ) 

Antifungal 

0.5-2% 

White powder 

Neutral 

Wide. Positive impact on esthetics and 
hair care benefits 

Ketoconazole 

Antifungal 

1-2% 

White powder 

Neutral 

Limited. Is expensive and requires 
regulatory approval 

Selenium sulfide 

Antifungal 

1-2% 

Red powder 

Sulfur-like 

Limited. Color and odor affect esthetics 

Moderately potent antifungal activity 





Climbazole 

Antifungal 

0.5-2% 

White powder 

Neutral 

Limited. Not accepted globally by 
regulatory bodies 

Octopirox 

Antifungal 

0.5-2% 

White powder 

Neutral 

Limited. Not accepted globally by 
regulatory bodies 

Sulfur 


1% 

Yellow powder 

Sulfur 

Limited. Color and odor affect esthetics 

Least potent antifungal activity 





Salicylic acid 

Keratolytic 

agent 

1.8-3.0% 

White powder 

Neutral 

Limited. Low antifungal potency 

Coal tar 

Regulator of 
keratinization 

0.5-1.0% 

Black viscous liquid 

Off-odor 

Limited. Color and odor affect esthetics 



Administration (FDA). Although the FDA does accept the 
safety and efficacy of salicylic acid, coal tar, and sulfur, either 
low potency or poor esthetics have limited their broad 
utilization. 


Unique attributes of scalp care products 

The complexity of the shampoo delivery vehicle described 
above in combination with the unique attributes of the 
active material accounts for varying levels of efficacy 
obtained when using similar actives at identical levels. The 
case is well-illustrated for shampoos based on PTZ, in which 
the physical form of the material as well as the shampoo 
composition affect resultant activity [1] by three parameters 
(Table 15.3). 

Regardless of the type of active material used in sham¬ 
poos, activity is derived from how much material is retained 
on the scalp surface after rinsing. This is a complex formula¬ 
tion technology task because cleaning is occurring simulta¬ 
neously. The efficiency of the coacervate technology delivery 
system directly impacts how much of a material such as PTZ 
is retained on the scalp after rinsing. This efficiency of this 
deposition can vary dramatically between commercial prod- 


Table 15.3 Formulation factors affecting the realization of full 
efficacy. 


1 Retention of active material on scalp after rinsing 

2 Physical bioavailability: spatial coverage of active on scalp surface 

3 Chemical bioavailability: prevalence of active species of active 


ucts and will directly affect efficacy [6]. The achievement of 
effective active delivery is a complex balancing of parame¬ 
ters to maximize delivery while not compromising the 
esthetic properties of the product. 

While the amount of material remaining on the scalp 
surface is critically important, the physical distribution and 
bioavailability of the material is just as important. For a 
particulate material such as PTZ, there is substantial technol¬ 
ogy in the optimization of the particle morphology (shape 
and size) to improve physical distribution on the scalp 
surface. There are two types of PTZ in use today. Standard 
PTZ has a submicron size and a nondescript morphologic 
shape. Optimized PTZ is used by one manufacturer where 
the morphology is platelet (Figure 15.3) and the particle size 
has been optimized to 2.5pm. Both of these parameters are 
designed to maximize the efficiency of scalp surface cover- 


118 










15. Shampoos 


age to achieve uniform benefits throughout the microenvi¬ 
ronment of the scalp. This is important as the effective zone 
around a PTZ particle (Figure 15.4a) is limited by the molec¬ 
ular solubility of PTZ in the surrounding medium of seba¬ 
ceous oils. By use of platelet morphology particles, the 



Figure 15.3 Electron micrograph of a unique form of pyrithione zinc 
(PTZ), optimized for size and morphology to maximize the efficiency of 
surface coverage. 


spatial coverage is more efficient than use of a three-dimen- 
sionally symmetric particle. Particle size of the platelet is also 
important to achieve uniformity of coverage. Ideally, smaller 
particles are better, but they suffer from a trade-off that they 
are more difficult to retain through the rinsing step. Thus, 
practically, it has been observed [1] that an optimum particle 
size is 2.5 pm, which represents the average size of the opti¬ 
mized PTZ material. Together, these attributes constitute 
physical bioavailability. 

The third factor affecting delivered efficacy is optimization 
of chemical bioavailability [7]. Chemically, PTZ is considered 
a coordination complex between inorganic zinc ion (Zn) and 
the pyrithione (PT) organic moiety. In such a material, the 
bonds are weak and an equilibrium exists between the intact 
species and the separate components (Figure 15.4b). Neither 
of the separated components (Zn and PT) are effective anti- 
fungals; thus, to the extent this dissociation occurs, PTZ 
chemical bioavailability and resultant efficacy is reduced. By 
adding a common ion to the system (in the form of zinc 
carbonate), the equilibrium is shifted (exploiting LeChatelier's 
principle) to the intact and more effective PTZ; this unique 
potentiated PTZ formula thus maximizes bioavailability of 
the deposited material. 

Another important aspect in product selection is that the 
cleaning activity of the shampoo not result in irritation of 



(b) 


Active 

species 


Standard PTZ formula 


Potentiated PTZ formula 



Figure 15.4 (a) Conceptual representation of the zone of inhibition of fungal growth surrounding PTZ particles and the importance of spatial 
distribution of particles to achieve uniformity of coverage, (b) PTZ can dissociate into component pyrithione (PT) and zinc (Zn) which reduces the 
presence of the intact bioactive species. The addition of zinc carbonate alters this equilibrium to maintain PTZ in its bioactive intact form. 


119 



















HYGIENE PRODUCTS Cleansers 


Table 15.4 Summary of advantages and disadvantages of using 
scalp care shampoos. 


Advantages 

Convenient form for treatment and prevention of dandruff/seborrheic 
dermatitis 

For cosmetically optimized therapeutics, compliance is increased 

• Affordability 

• No esthetic trade-offs 

For PTZ-based products, over 50 years of safe utilization 
For PTZ-based products, no tachyphylactic responses 

Disadvantages 

For straight therapeutic products, compliance is reduced 

• Can be very expensive 

• Can have substantial esthetic trade-offs 


the scalp. For those with D/DS this would interfere with the 
natural cutaneous repair processes that occur upon Malassezia 
population reduction. In addition to appropriate selection of 
the surfactant system as described above, some antifungal 
actives such as PTZ have been shown to reduce the irritation 
potential of the surfactants [8]. 


Advantages and disadvantages 

The use of therapeutic shampoos for effective treatment of 
D/SD as well maintenance of normal scalp hygiene is very 
convenient because the patient will be utilizing this product 
in the shower already (Table 15.4). By choice of a cosmeti¬ 
cally optimized therapeutic product, the user suffers no 
esthetic trade-offs (compared to cosmetic shampoos) that 
would limit compliance. This class also tends to be more 
affordable than standard therapeutic products, which also 
increases long-term (prophylactic) usage. No diminution of 
benefit (e.g. tachyphylaxis) occurs upon long-term use of 
PTZ-based products; this is based on both designed clinical 
studies [9] as well as anecdotal evidence associated with 
over 50 years of usage history. The only disadvantage of 
using such scalp care products occurs when a strict thera¬ 
peutic product is chosen. The expense and esthetic negatives 
that normally accompany such products limit patient com¬ 
pliance leading to frequent frustrating condition reoccur¬ 
rence; these products should be limited to the most 
recalcitrant of cases. 


Effective use of products 

D/SD is a chronic condition characterized by frequent reoc¬ 
currence, resulting in frustration on the part of the patient 
(Table 15.5) [10]. Initial treatment of the condition appears 


Table 15.5 Summary of usage habits to maximize the therapeutic 
benefit. 


1 Use the therapeutic shampoo for every shampooing to prevent a 
relapse 

2 Use a therapeutic product that is cosmetically optimized and 
affordable 

3 Shampoo as frequently as possible 

4 Lather exposure time is not important but repeating the entire 
process can be beneficial 

5 Product should be utilized all year 

6 If a rinse-off conditioner is needed, use one that contains 
antidandruff active 


to be managed fairly effectively by either independent use 
of therapeutic antifungal shampoos or by combination with 
topical corticosteroid usage. However, preventative treat¬ 
ment is required for long-term management of the condi¬ 
tion. Because Malassezia easily recolonize, using a cosmetically 
optimized therapeutic product for each shampoo experience 
is the optimum method for preventing reoccurrence. 

If cosmetic shampoo usage is interspersed with therapeu¬ 
tic products, efficacy is decreased [11]; not only does the 
cosmetic shampoo not deliver active to the scalp, it washes 
off any deposited material from the prior exposure to the 
active-containing shampoo. The desire to switch between a 
cosmetic shampoo and therapeutic product is either the real 
or perceived esthetic trade-offs in use of a therapeutic 
product. It has been shown [12] that therapeutic products 
do not provide all of the desired esthetic benefits and that 
this will drive patients to choose cosmetically optimized 
therapeutic shampoos for treating scalp conditions. Even 
with cosmetically optimized therapeutic products, there is 
often a perception that these products are not equivalent to 
cosmetic shampoos. While this may have been true in the 
past, modern technologies can deliver efficacious therapeu¬ 
tic and cosmetic benefits without the traditional trade-offs 
of standard therapeutic treatments. 

A wide range of D/SD shampoo treatments are available 
[13], with widely ranging costs. By recommending a thera¬ 
peutic product that has been cosmetically optimized and one 
that is affordable for ongoing usage, the patient is best 
advised to use this product as their normal product to 
prevent reoccurrence. 

Even by selection of an effective therapeutic product, how 
it is used can make a difference to the magnitude of benefit 
achieved. The length of time the lather is exposed to the 
scalp is generally not important as it is the material that is 
retained on the scalp after rinsing that provides the benefit. 
Using coacervate-based deposition technologies, it is the 
rinsing that triggers the deposition. Repeating the lathering 
and rinsing process twice will more thoroughly remove the 
sebaceous lipid and allow more active to be deposited. 


120 








15. Shampoos 


D/SD symptoms occur year-round and should be treated 
all year. There is a misperception that it is a seasonal condi¬ 
tion, primarily occurring in cold, dry seasons. This has been 
shown not to be true ini. Winter months with less humid 
air combined with the tendency to wear darker clothing 
make the patient more able to detect the flaking symptoms 
under these conditions, but they occur all of the time. Higher 
frequency of shampooing may occur in summer months 
resulting in a slight decrease in severity of symptoms. 

Another critical usage factor involves whether a rinse-off 
conditioner is used after the shampoo [11]. Rinse-off condi¬ 
tioners that do not contain antidandruff actives remove a 
portion of the deposited active from the prior therapeutic 
shampoo exposure thereby reducing efficacy. If the patient 
desires use of a rinse-off conditioner, one containing anti¬ 
dandruff active should be recommended so that loss of 
retained active does not occur once the entire hair care 
regimen is practiced. 


Benefits of use of scalp care shampoos 

Resolution of D/SD is the primary motivation for initiation 
of use of therapeutic shampoos. The choice of shampoo 
should be motivated by, in order: efficacy, cosmetic hair 
benefits, and cost. Assessing the relative efficacy of a product 
usually involves double-blind placebo-controlled drug 
studies using medical experts to grade the severity of flaking 
and erythema. A review of the comparative efficacy of prod¬ 
ucts [3] supports that the most effective products are those 
that contain an effective antifungal, the most potent of 
which are PTZ, selenium sulfide, and ketoconazole. Further 
rank-ordering within this group is somewhat difficult 
because of conflicting studies and the part that the specific 
formulation then plays. However, it is clear that cosmetically 
optimized therapeutics can be as effective as standard thera¬ 
peutics; the marketing strategy used to position these prod¬ 
ucts is not necessarily a good predictor of the true technical 
efficacy. 

The use of certain scalp care shampoos also demonstrate 
the ability to deliver anti-irritancy effects [14]. There appears 
to be a wide range in activities depending on the specific 
active used. PTZ, and especially the potentiated PTZ formula, 
appears to be most effective at reducing irritation. Irritation 
and inflammation are early steps in the etiology of D/SD as 
well as many other scalp conditions. Thus, use of the zinc- 
based therapeutic products may well have general scalp 
health benefits beyond D/SD mitigation [15]. 

The scalp health benefits associated with use of antidan¬ 
druff shampoos may extend to hair benefits as well. A 
number of studies have demonstrated (e.g. Berger etal. [16]) 
that use of these products can reduce the rate at which hair 
is lost. The mechanism for this benefit is not known, but 
may be speculated to originate in the reduction of inflam¬ 


mation referred to above as follicular inflammation may 
impede regrowth of lost hairs. A further benefit of the scalp 
inflammation being reduced by these products is less itch 
and subsequent scratching which reduces hair damage and 
improves the quality and appearance of hair. 


Conclusions 

Normal scalp hygiene requires frequent and effective clean¬ 
ing of the scalp. Cosmetic shampoos do this effectively while 
providing conditioning benefits for the hair. For many indi¬ 
viduals, this frequent cleaning is sufficient to prevent adverse 
scalp effects. However, many still experience the symptoms 
of D/SD. For this group, therapeutic products are required 
that contain antidandruff actives that control the scalp 
Malassezia population. A subset of this class is cosmetically 
optimized therapeutics in which the product delivers the 
therapeutic benfits without loss of the typical cosmetic 
shampoo esthetics. This leads to much higher compliance, 
leading to effective long-term care of the chronic condition. 
Other factors relevant for selecting the most useful product 
are that the active and shampoo composition be optimized 
to maximize the physical and chemical bioavailability of the 
active; this is especially true for PTZ-based treatments. Once 
the best shampoo is chosen, effective habits are required to 
realize the full benefit: frequent use without switching 
to cosmetic shampoos, use all year around, and the use 
of a rinse-off conditioner that also contains antidandruff 
active. 

References 

1 Schwartz J. (2007) Treatment of seborrheic dermatitis of the 
scalp. J Cosmet Dermatol 6, 18-22. 

2 Elewski B. (2005) Clinical diagnosis of common scalp disorders. 
J Investig Dermatol Symp Proc 10, 190-3. 

3 Schwartz J, Cardin C, Dawson T Jr. (2005) Dandruff and sebor¬ 
rheic dermatitis. In: Barran R, Maibach H, eds. Textbook of Cosmetic 
Dermatology, 3rd edn: New York: Taylor & Francis, pp. 259-72. 

4 Shaw E, Bernstein J, Losee K, Lott W. (1950) Analogs of aspergil- 
lic acid. IV. Substituted 2-bromopyridine-N-oxides and their 
conversion to cyclic thiohydroxamic acids. J Am Chem Soc 72, 
4362-4. 

5 Snyder F. (1969) Development of a therapeutic shampoo. Cutis 
5, 835-8. 

6 Bailey P, Arrowsmith C, Darling K, Dexter J, Eklund J, Lane A, 
etal. (2003) A double-blind randomized vehicle-controlled clini¬ 
cal trial investigating the effect of ZnPTO dose on the scalp vs. 
antidandruff efficacy and antimicotic activity. Int J Cosmet Sci 25, 
183-8. 

7 Schwartz J. (2005) Product pharmacology and medical actives 
in achieving therapeutic benefits. J Investig Dermatol Symp Proc 
10, 198-200. 

8 Warren R, Schwartz J, Sanders L, Juneja P. (2003) Attenuation 
of surfactant-induced interleukin la expression by zinc 
pyrithione. Exog Dermatol 2, 23-7. 


121 




HYGIENE PRODUCTS Cleansers 


9 Schwartz J, Rocchetta H, Asawanonda P, Luo F, Thomas J. 
(2009) Does tachyphylaxis occur in long-term management of 
scalp seborrheic dermatitis with pyrithione zinc-based treat¬ 
ments? Int J Dermatol 48, 79-85. 

10 Chen S, Yeung J, Chren M. (2002) Scalpdex: a quality-of-life 
instrument for scalp dermatitis. Arch Dermatol 138, 803-7. 

11 Schwartz J. (2004) A practical guide for the treatment of dan¬ 
druff and seborrheic dermatitis. J Am Acad Dermatol 50, P71. 

12 Draelos Z, Kenneally D, Hodges L, Billhimer W, Copas M, 
Margraf C. (2005) A comparison of hair quality and cosmetic 
acceptance following the use of two anti-dandruff shampoos. 
J Investig Dermatol Symp Proc 10, 201-4. 


13 Schwartz R, Janusz C, Janniger C. (2006) Seborrheic dermatitis: 
an overview. Am Fam Physician 74, 125-30. 

14 Margraf C, Schwartz J, Kerr K. (2005) Potentiated antidandruff/ 
seborrheic dermatitis formula based on pyrithione zinc delivers 
irritation mitigation benefits. J Am Acad Dermatol 52, P56. 

15 Schwartz J, Marsh R, Draelos Z. (2005) Zinc and skin health: 
overview of physiology and pharmacology. Dermatol Surg 31, 
837-47. 

16 Berger R, Fu J, Smiles K, Turner C, Schnell B, Werchowski K, 
et al. (2003) The effects of minoxidil, 1% pyrithione zinc and a 
combination of both on hair density: a randomized controlled 
trial. Br J Dermatol 149, 354-62. 


122 


Part 2: Moisturizers 


Chapter 16: Facial moisturizers 

Yohini Appa 

Johnson & Johnson, New Brunswick, NJ, USA 


BASIC CONCEPTS 

• Facial moisturizers can be used to improve skin texture, treat dry skin, and provide sun protection. 

• Occlusives, humectants, emollients, and sunscreens are important ingredient categories in facial moisturizers. 

• The efficacy of a facial moisturizer can be measured via transepidermal water loss and corneometry. 

• Facial moisturizers can be an important adjunct in the treatment of facial dermatoses, such as atopic dermatitis and eczema. 


Introduction 

The face is the most conspicuous representation of age and 
health. While the eyes are considered the windows to the 
soul, the face is its billboard. No other body part demon¬ 
strates personal past history as convincingly as the face. 
Wrinkles form on the face well before the rest of the body 
and serve as an indicator of age and lifestyle. The relative 
color and luminosity of the facial skin represents overall 
health and emotional state. Facial skin can be dull to vibrant 
representing poor to excellent physical health. The face 
mirrors acute changes in well-being. For example, persons 
experiencing cardiac distress appear "ashen" while anger or 
embarrassment may be expressed as a reddened face. Thus, 
the face represents the current physical state of the indi¬ 
vidual. Moisturizers can enhance the appearance of the face 
and are thus important cosmeceuticals. 

The face is rarely covered and constantly subjected to the 
elements. It is one of the most light-exposed areas of skin 
on the body, the other areas being the shoulders, upper 
chest, and forearms; as a result it receives high amounts of 
UV radiation. The incidence of cutaneous melanoma as 
measured by relative tumor density is highest on the face in 
subjects over the age of 50 years, a statistic that is interpreted 
as directly correlating to the amount of long-term UV expo¬ 
sure [1]. This means that facial photoprotection is of great 
importance, thus the incorporation of efficacious UVA and 
UVB protection in daily facial moisturizers is worthwhile. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Facial skin is physiologically unique. It possesses numer¬ 
ous sweat glands and a relatively thin dermis. It is densely 
populated with sebaceous glands, possessing 400-900 glands 
per square centimeter [2]. The face is a major point of 
contact for sensory input, the facial skin possesses high 
innervation and is therefore more sensitive than skin else¬ 
where on the body [3]. The skin covering the face also has 
to allow for the subtleties of facial expressions and pho- 
noation. Of all the areas on the body, the skin on the face 
has the highest level of hydration. When the ratio of tran¬ 
sepidermal water loss (TEWL) to skin surface hydration was 
calculated in order to determine the most consistently 
hydrated area of the body, the forehead and cheek showed 
the lowest ratios (Figure 16.1). 


Dry facial skin 

Dry skin is a term used to describe the condition that arises 
when the normal functioning of the skin is compromised. 
More specifically, it is a manifestation of the consequences 
that arise from a loss of water from the outermost layer of 
the dermis: the stratus corneum (SC). The SC is formed 
when keratinocytes, cuboidal cells in the lower half of the 
epidermis, migrate from the basal layer to the most superfi¬ 
cial layer, producing large amounts of the water-insoluble 
protein keratin along the way. The keratinization and migra¬ 
tion process results in flattened, keratin-filled keratinocytes, 
referred to as corneocytes, which create an overlapping 
barrier with a "brick and mortar" appearance that is nearly 
waterproof. The gaps between the corneocytes, or "bricks," 
are filled with intercellular lipids, or "mortar" that is pro¬ 
duced by keratohyaline granules. The SC layer is also 


123 









HYGIENE PRODUCTS Moisturizers 


Forehead 



Figure 16.1 Skin surface hydration and transepidermal water loss 
(TEWL) and SciCon ratio. 

referred to as the "dead layer" because by this point the cells 
have stopped synthesizing proteins and are unresponsive to 
cellular signaling. Cells in the SC are eventually sloughed 
off and replaced by more cells coming up through the epi¬ 
dermis, thereby maintaining a continuous barrier. It nor¬ 
mally takes 26-42 days for the epidermis to cycle completely 
[4]. 

The process of skin cell differentiation and maturation is 
a delicate balance that is easily disrupted. If the water 
content of the SC drops below 20% for an extended period 
of time, the enzymes involved in desquamation will be 
unable to function and the process of orderly epidermis 
cycling will be compromised. This especially apparent in dry 
facial skin. 

There are many functions that the epidermal barrier 
performs: 

1 Maintains a 20-35% water content; 

2 Limits TEWL; 

3 Preserve water homeostasis in the epidermis; 

4 Sustains optimal lipid synthesis; and 

5 Allows for orderly desquamation of SC cells. 


A shift away from equilibrium in one of these five functions 
can result in a compromise of the barrier and the basic con¬ 
sequence is what we refer to as "dry skin." More specifically, 
when TEWL is increased to the point that the water content 
in the SC is reduced to below 10%, the clinical signs of 
xerosis will appear [5]. 

The orderly desquamation of the SC is a complex process 
which if disturbed can lead to a self-renewing cycle of dry 
skin. The corneocytes that make up the SC are highly 
interconnected and able to withstand a large amount of 
mechanical stress. When new cells are formed, enzymatic 
digestion of the proteins anchoring the old cells is required 
for removal. The level of humidity in the SC is a critical 
factor modulating the activity of these desquamatory 
enzymes, specifically stratum corneum chymotryptic enzyme 
(SCCE). When this process breaks down, desquamation 
becomes irregular and dead SC cells slough off in large 
clumps; representing the "flaking" seen in so many dry facial 
skin conditions [6]. 

The sebum-rich skin of the face can appear moisturized 
but possess a low water content. Sensory symptoms can 
include but are not limited to: dryness, discomfort, pain, 
itching, stinging, or tingling sensations. Tactile signs are 
rough, uneven, and sand-like feeling skin. Visible signs, 
which can be macroscopic or microscopic, are redness, dull 
surface, dry white patches, flaky appearance, and cracks and 
fissures. There are many causes for these signs and symp¬ 
toms. In all, the presence of dry skin represents disorder 
in the complex system that continually renews the facial 
skin. 


Facial moisturization 

The physiologic goal of facial moisturization is to restore the 
elasticity and flexibility of the SC, thereby restoring its 
barrier function. Additionally, the reintroduction of humid¬ 
ity to the SC allows for proper functioning of desquamation 
enzymes and restores the natural skin renewal cycle. 
Kligman and Leyden [7] defined a moisturizer as "a topically 
applied substance or product that overcomes the signs and 
symptoms of dry skin." The esthetic goal of moisturization 
is achieving soft, supple, glowing, healthy looking skin, as 
subjectively evaluated by the end-user. Regular use of facial 
moisturizers mitigate and prevent signs of aging, especially 
when formulated with broad-spectrum sun protection for 
daytime use. 

Because the face is one of the most sensitive areas of the 
body, a facial moisturizer must meet esthetic goals in addi¬ 
tion to fulfilling a broad set of performance attributes. 
Consumers expect a facial moisturizer to reduce dryness, 
improve dull appearance, smooth and soften the skin, and 
increase suppleness [8]. Furthermore, these expectations 


124 



























16. Facial moisturizers 


Table 16.1 Function of common moisturizer ingredients. This listing represents the common ingredients found in a moisturizer formulation 
identifying the role of each of the substances in the ingredient disclosure. 



Humectant 

Emollient 

Occlusive 

Emulsifier 

Preservative 

Dimethicone 


X 

X 



Trisiloxane 


X 




Glycerin 

X 

X 




Glyceryl stearate 




X 


PEG 100 stearate 




X 


Potassium cetyl phosphate 




X 


Behenyl alcohol 



X 



Caprylyl methicone 


X 




Hydrogenated palm glycerides 


X 




Hexanediol 

X 

X 




Caprylyl glycol 

X 

X 




Cetearyl glucoside 



X 



Cetearyl alcohol 



X 



Methylparaben 





X 

Propylparaben 





X 

Methylisothiazolinone 





X 


must be achieved by a moisturizer with a minimal presence 
and pleasant sensory qualities. 

A properly formulated moisturizer can supplement the 
function of the endogenous epidermal lipids and restore the 
epidermal barrier function. This allows the skin to continue 
its natural process of renewal and desquamation at a normal 
rate. The substances utilized by all moisturizers to achieve 
this desired effect fall into a handful of basic categories (Table 
16.1). Humectants, such as glycerin, attract and hold mois¬ 
ture, facilitating hydration. Emollients, typically lipids or 
oils, enhance the flexibility and smoothness of the skin and 
provide a secondary soothing effect to the skin and mucous 
membranes. Occlusives create a hydrophobic barrier to 
reduce water loss from the skin. Emulsifiers work to bring 
together immiscible substances; they are a critical element 
in the oil and water mixtures employed in moisturizer for¬ 
mulas. Preservatives prevent the premature breakdown of 
components and inhibit microbiologic growth. Fragrances 
not only add to the esthetic value but can also mask the odor 
of formulation ingredients. 

These components make up the basic formulation of any 
moisturizer, and the choices available to achieve the pre¬ 
ferred outcome are vast. The formulation of an acceptable 
and effective moisturizer for the face, one that will enable 


the natural processes of skin desquamation to occur and 
maintain healthy barrier function while meeting high 
esthetic standards, is as much an art as it is a science. 


Facial moisturizer formulation 

Facial moisturizers are typically oil-in-water emulsions. The 
water improves skin feel and offers an acceptable, univer¬ 
sally tolerated base for the active ingredients. The water or 
oil solubility of components is inconsequential because both 
are present. Emulsions allow for a wide range of properties, 
such as slow to fast absorption rates depending on the final 
viscosity of the formulation. The fine-tuning of these prop¬ 
erties is important for achieving the high esthetic expecta¬ 
tions of a facial moisturizer. For example, a daily-use formula 
with high emollient content may feel heavy in a cream but 
be acceptable in liquid form. Conversely, overnight creams 
with antiaging additives may be thick in order to remain on 
the face during sleep and to slow the absorption of active 
components. Therefore, by utilizing a range of water to oil 
ratios, and varying humectant and emollient mixtures, the 
desired effects can be formulated within the acceptable 
esthetic parameters for a facial moisturizer. 


125 






hygiene PRODUCTS Moisturizers 


Moisturizer ingredients and function 

Humectants 

The overall hydration level of the SC affects its mechanical 
properties. If the water level in the SC drops below 10%, its 
flexibility can be compromised and it becomes susceptible to 
damage from mechanical stress [9]. Humectants are key 
substances to maintain skin hydration. Natural humectants, 
such as hyaluronic acid, are found in the dermis, but exter¬ 
nal humectants can be externally applied in moisturizers. 
Humectants draw water from the viable epidermis and 
dermis, but can draw water from the environment if the 
ambient humidity is over 80%. 

Humectants are water-soluble organic compounds that 
can sequester large numbers of water molecules. Glycerin, 
sorbitol, urea, and sodium lactate are all examples of exter¬ 
nally applied humectants. Glycerin, also referred to as glyc¬ 
erol, is one of the most widely utilized compounds in 
cosmetic formulations because of its effects on multiple 
targets and its universal applications. Its chemical structure 
brings together the stability of three carbon atoms with three 
water-seeking oxygen atoms in an anisotropic molecule that 
is perfectly designed for use in skin and hair moisturizers. 
Glycerin also allows for the construction of different product 
physical forms that cover the spectrum from sticks to micro- 
emulsions to free-flowing creams that maintain stability 
over time. 

The degree of purity to which glycerin can be manufac¬ 
tured not only ensures consistency and facilitates microbio- 
logic stability, but also guarantees the minimization of allergic 
reactions by contaminants. The pure form of glycerin has 
been tested on thousands of patients and millions more have 
used it with extremely few reports of ill effects. Glycerin is 
generally classified as a humectant; however, this character¬ 
istic is not the sole reason for its ability to achieve skin mois- 
turization, in fact, it performs a number of different functions 
that are not directly related to its water-holding properties. 

Glycerin can restore the suppleness of skin without 
increasing its water content, a trait that is exploited by its 
use in the cryopreservation of skin, tissue, and red blood 
cells, where water would freeze and damage them. Glycerin 
enhances the cohesiveness of the intercellular lipids when 
delivered from high glycerin therapeutic formulations, 
thereby retaining their presence and function. Furthermore, 
glycerin has been identified as a contributor to the process 
of desquamation, a critical component of the dermal renewal 
cycle, through its ability to enhance desmosome digestion. 

In addition to its direct, humectant effects on skin mois- 
turization, endogenously produced glycerin has exhibited 
effects at the molecular level in knockout mouse model 
studies, confirming its role in maintaining SC hydration and 
barrier maintenance. A recent study showed that glycerin 
content was three times lower, SC hydration was reduced. 


and barrier function was impaired in mice deficient in the 
water/glycerin transporter protein, aquaporin-3 (AQP3) 
despite normal SC structure, protein-lipid composition and 
ion-osmolyte content. Glycerin, but not other small poly 
glycols, restored normal SC moisturization and TEWL values 
when applied to the AQP3-deficient mice, confirming that 
glycerin was physiologically necessary in the modulation of 
SC hydration and barrier maintenance [10]. 

Glycerin remains the gold standard for moisturization. 
The fact that it acts on so many different parameters with 
a nearly non-existent side-effect profile makes it a prime 
candidate for facial moisturizer formulations. It is also an 
excellent example of how moisturizer components, espe¬ 
cially those used on the face, should be considered for their 
ability to enhance and protect the skin. Glycerin raises the 
bar for moisturizers in that it is capable of enhancing, or 
even rescuing, the intrinsic processes that are in place to 
maintain the orderly maturation of keratinocytes and the 
barrier function of the skin. 

Occlusives 

Humectants are only partially effective in moisturizing the 
skin. In order to maintain epidermal water content and 
preserve the barrier function of the SC, occlusive agents are 
employed in a role meant to complement the water-attract¬ 
ing nature of humectants. Occlusive agents inhibit evapora¬ 
tive water loss by forming a hydrophobic barrier over the 
SC and its interstitial areas. Occlusion is successful in the 
treatment of dry skin because the movement of water from 
the lower dermis to the outer dermis is a guaranteed source 
of physiologically available water. Moreover, these occlusive 
agents have an emollient effect, as is the case with behenyl 
alcohol. 

Petrolatum and lanolin are two historically popular occlu¬ 
sives that are slowly being replaced by more sophisticated 
alternatives. Petrolatum is a highly effective occlusive, but 
it suffers from an unfavorable esthetic. Lanolin is not recom¬ 
mended for use in facial formulations because of its odor 
and potential allergenicity [11]. Newly constructed silicone 
derivatives have been employed in moisturizers for their 
occlusive properties, and they further enhance the esthetic 
quality of the formulation by imparting a "dry" touch. This 
technologic advancement is also an example of how the 
esthetic parameter of a facial moisturizer can have a major 
effect on compliance and willingness to apply. 

Emollients 

Emollients are agents, usually lipids and oils, designed to 
soften and smooth the skin. Lipids are non-polar molecules 
and as such they repel polarized water molecules, thereby 
limiting the passage of water to the environment. The most 
prevalent lipids in the SC, especially within the extracellular 
membranes, are ceramides. They comprise about 40% of the 
lipid content of the SC, the remainder of which is 23% 


126 



16. Facial moisturizers 


cholesterol, 10-15% free fatty acids, and smaller quantities 
of triglycerides, stearyl esters, and cholesterol sulfate. These 
lipids are synthesized throughout the epidermis, packaged 
in lamellar granules, and eventually differentiate into 
multilamellar sheets that form the ceramide-rich SC water 
barrier [12]. 

The purpose of an emollient is to replace the absent 
natural skin lipids in the space between the corneocytes in 
the SC. Additional benefits include the smoothing of rough¬ 
ened skin thereby changing the skin's appearance, and 
providing occlusion to attenuate TEWL and enhance mois- 
turization. Of the three components of skin moisturizers 
listed in the CTFA Cosmetic Ingredients Directory, emol¬ 
lients outnumber occlusives 2 to 1 and the humectants 10 
to 1. This is an indication not only of the number of available 
compounds that can perform this function, but also the 
variety of lipids that can be utilized [13]. 

Fragrance 

Fragrance is a component of facial moisturizers that is often 
dismissed as an unnecessary potential irritant, but this idea 
is becoming increasingly antiquated as the science support¬ 
ing its proper use and evaluation is improved. Vigorous 
protocols have been developed that comprehensively and 
conclusively assess the tolerance of formulations on human 
subjects. Fragrances are screened separately first and then 
together in both normal and sensitive populations, and 
utilized at the minimum concentration required to mask 
the smell of certain components, if necessary. Fragrance 
improves the overall esthetic qualities of the moisturizer, 
which is an important component of any moisturizer for¬ 
mulation, especially one that is applied to the face. 

Preservatives 

Preservatives are also subject to the same rigorous testing 
protocols as fragrances. The preservative must be strong 
enough to completely inhibit bacterial growth, but must not 
be sensitizing or irritating. Preservatives are an important 
component in facial moisturizers to prevent the lipids in the 
formulation from becoming rancid. All facial moisturizers 
have some type of preservative, because there is really no 
such thing as a preservative-free formulation. 

Photoprotection and facial moisturizers 

Sunscreens could be considered to be the most globally 
effective ingredient added to a facial moisturizer. Because 
the incidence and mortality rates of skin cancer have been 
steadily rising in the USA, the use of sunscreen as a daily 
protectant has become more important to consumers. There 
are both immediate and long-term benefits from photopro¬ 
tection. The immediate benefit is the prevention of a painful 
sunburn while long photoprotection results in reduced 
photodamage manifesting as wrinkling, inflammation, and 
dryness. 


A key immediate event that leads to chronic photoaging 
is the production of proteases in response to UV irradiation 
at doses well below those that cause skin reddening. Matrix 
metalloproteinases (MMPs), for example, are zinc-depend¬ 
ent endopeptidases expressed in many different cell types 
and are critical for normal biologic processes. They may also 
be involved in desquamation processes, and overexpression 
would lead to early sloughing and increase in TEWL. With 
a proper sunscreen regimen, production of MMPs is mini¬ 
mized and their participation in chronic photoaging can be 
avoided. The addition of sunscreens to facial moisturizers 
also contributes to the prevention of reactive oxygen species 
(ROS) production, Langerhans cell depletion, and sensitivity 
to UV radiation, as is observed in polymorphous light 
eruption. 


Facial moisturizer testing 

The formulation of a moisturizer centers on the primary goal 
of delivering the perception of moisture to the skin. This 
includes not only adding moisture to the skin, but also the 
improvement of the barrier function and reinstating natural 
skin reparative processes. The testing of the efficacy of a 
moisturizer is based on barrier function assessment. 

There are many ways to assess the barrier function of the 
skin based on SC integrity. Measurement of the TEWL is one 
method. A damaged SC allows water to evaporate resulting 
in high TEWL readings. These measurements are taken with 
an evaporimeter, which measures the amount of water 
vapor leaving the skin. The amount of water in the skin can 
also be measured via skin conductance. This technique, 
known as corneometry, measures the amount of low level 
electricity conducted by the skin. Because water is the con¬ 
ductor of electricity in the skin, the amount of current con¬ 
ducted is directly related to the water content. Thus, the 
efficacy of a moisturizer can be measured by its effect on 
water vapor loss and skin conductance. 

Another method for evaluating skin dryness is D-squames. 
D-squames are circular, adhesive discs placed on the skin 
surface with firm pressure and then pulled away. The 
removed skin is observed and parameters such as the amount 
of skin removed, size of flakes, and coloration can be 
recorded. Differences between dry skin and normal moistur¬ 
ized skin are clearly evident upon examination of the disc, 
and further characterization can be carried out to differ¬ 
entiate levels of dryness and qualitative differences in 
desquamation. 

The barrier function of the skin can be assessed following 
application of an irritant to the skin surface. The introduc¬ 
tion of an irritant can cause erythema and scaling in the 
compromised SC. A frequent irritant used for the assessment 
of barrier function is sodium lauryl sulfate (SLS). The 
amount of erythema and TEWL is measured following 


127 



HYGIENE PRODUCTS Moisturizers 


scrubbing of the skin with SLS. Skin with a better barrier 
following use of an efficacious moisturizer will experience 
less damage than skin that possesses a compromised barrier. 

Finally, after testing the efficacy of the formulation in a 
controlled, laboratory setting, its efficacy must be evaluated 
on a group of consumers. Consumer testing is usually carried 
out in a blind study involving 200-300 subjects, from geo¬ 
graphically disparate locales in order to normalize any dif¬ 
ferences in skin types or backgrounds. This testing will 
introduce parameters that are evaluated subjectively by the 
population of subjects such as skin feel, perception of 
texture, ease of application, and scent, among other things, 
that define its esthetic qualities. The functional qualities of 
the moisturizer, such as "immediate comfort" and "long- 
lasting effect" will also be evaluated by the consumer group 
and incorporated into the overall assessment. 


Use of facial moisturizers in common 
inflammatory dermatoses 

The face presents a set of unique challenges regarding the 
treatment of skin disorders. What may be acceptable for 
treatment regimens elsewhere on the body, such as a strong 
occlusive such as petrolatum or a humectant such as urea, 
will be esthetically challenging to the user and stand in the 
way of compliance. While it is easy to think of esthetics as 
secondary to efficacy of treatment, it should be considered 
of primary importance where the face is concerned. This 
concept cannot be overstressed because the sensitivity of the 
facial skin to the sensory and olfactory qualities of moistur¬ 
izers is much higher than the rest of the body. 

It is generally believed that facial atopic dermatitis and 
various other facial skin diseases are associated with distur¬ 
bances of skin barrier function as evidenced by an increase 
in TEWL, a decrease in water-binding properties, and a 
reduction in skin surface lipids. When chronic, inflamma¬ 
tory skin diseases manifest on the face, there is the challenge 
of reducing the lesion as quickly as possible to prevent it 
from worsening and further compromising the integrity of 
the skin involved. Because of the high sensitivity of the facial 
skin, what may start as a small lesion can quickly be exac¬ 
erbated through physical intervention and quickly wors¬ 
ened. These problems can be addressed through the continual 
use of appropriate moisturizers, which have been shown to 
improve skin hydration, reduce susceptibility to irritation, 
and restore the integrity of the SC. Some moisturizers also 
supply the compromised SC with lipids that further acceler¬ 
ate barrier recovery. Moisturizers can serve as an important 
first-line therapeutic option for patients with atopic derma¬ 
titis and other chronic skin diseases [14]. 

Historically, moisturizers have been shown to have a ster¬ 
oid-sparing effect in patients with atopic dermatitis and 
eczema. Many of the elements in moisturizers, from lipids 


to emollients, have been shown to significantly improve the 
condition of the skin when used by patients with various 
dermatoses [15]. Glycerin has been implicated in the molec¬ 
ular mechanism controlling keratinocyte maturation, an 
important aspect of normal desquamation and barrier main¬ 
tenance. Furthermore, its role in maintenance of hydration 
for the proper functioning of proteases, especially filaggrin, 
is critical to the successful treatment of eczemas [16,17]. 

Recently, a comprehensive clinical study provided evi¬ 
dence that moisturizers not only enhance the efficacy of 
topical corticosteroids in patients with atopic dermatitis, but 
may also prevent the recurrence of disease [15]. In general, 
the maintenance of the SC along with rapid repair of disrup¬ 
tions to the barrier that would otherwise become larger and 
increase inflammation and discomfort as well seem to be 
central tenets in the approach to treating potential derma¬ 
toses on the face with moisturization. Therefore, facial mois¬ 
turizers may represent a valuable first-line treatment option 
for many dermatologic diseases and confer a number of 
important therapeutic benefits that go beyond the surface of 
the facial skin and have a critical role in the molecular 
mechanisms that maintain healthy skin. 


Conclusions 

Facial moisturizers fulfill an important need by providing 
skin comfort and alleviating dryness. Efficacious formula¬ 
tions contain ingredients that work directly to bring mois¬ 
ture to the skin, but also indirectly, as is the case with 
glycerin, induce the transport and retention of water mol¬ 
ecules at the subcellular level. The goal of facial moisturizers 
is to enhance, or restart, the processes intrinsic to the skin's 
natural ability to maintain its barrier function through the 
multiple pathways utilizing proteases, lipids, cell differentia¬ 
tion and, eventually, desquamation, all while maintaining 
an esthetically pleasant presence. 

References 

1 Elwood JM, Gallagher RP. (1998) Body site distribution of cuta¬ 
neous malignant melanoma in relationship to patterns of sun 
exposure. Int J Cancer 78, 276-80. 

2 Montagna W. (1959) Advances in Biology of Skin. Oxford, New 
York: Symposium Publications Division, Pergamon Press. 

3 Montagna W, Kligman AM, Carlisle KS. (1992) Atlas of Normal 
Human Skin. New York: Springer-Verlag. 

4 Baumann L. (2002) Cosmetic Dermatology: Principles and Practice. 
New York: McGraw-Hill. 

5 Draelos ZK. (2000) Atlas of Cosmetic Dermatology. New York: 
Churchill Livingstone. 

6 Watkinson A, Harding C, Moore A, Coan P. (2001) Water modu¬ 
lation of stratum corneum chymotryptic enzyme activity and 
desquamation. Arch Dermatol Res 293, 470-6. 

7 Kligman AM, Leyden JJ. (1982) Safety and Efficacy of Topical Drugs 
and Cosmetics. New York: Grune & Stratton. 


128 




16. Facial moisturizers 


8 Barton S. (2002) Formualtion of skin moisturization. In: Leyden 
JJ, Rawlings AV, eds. Skin Moisturization. New York: Marcel 
Dekker, pp. 547-84. 

9 Rawlings AV, Canestrari DA, Dobkowski B. (2004) Moisturizer 
technology versus clinical performance. Dermatol Ther 17 (Suppl 
1), 49-56. 

10 Hara M, Verlcman AS. (2003) Glycerin replacement corrects 
defective skin hydration, elasticity, and barrier function in 
aquaporin-3-deficient mice. Proc Natl Acad Sci USA 100, 
7360-5. 

11 Draelos ZK. (1995) Cosmetics in Dermatology , 2nd edn. New York: 
Churchill Livingstone. 

12 Downing S, Stewart ME. (2000) Epidermal composition. In: 
Loden M, Maibach HI, eds. Dry Skin and Moisturizers: Chemistry 
and Function. Boca Raton: CRC Press, 2000: pp. 13-26. 

13 Draelos ZK, Thaman LA. (2006) Cosmetic Formulation of Skin Care 
Products. New York: Taylor & Francis. 

14 Lebwohl M. (1995) Atlas of the Skin and Systemic Disease. New 
York: Churchill Livingstone. 

15 Ghali FE. (2005) Improved clinical outcomes with moisturiza¬ 
tion in dermatologic disease. Cutis 76 (Suppl), 13-8. 

16 Hanifin JM. (2008) Filaggrin mutations and allergic contact sen¬ 
sitization. J Invest Dermatol 128, 1362-4. 

17 Presland RB, Coulombe PA, Eckert RL, et al. (2004) Barrier 
function in transgenic mice overexpressing K16, involucrin, 
and filaggrin in the suprabasal epidermis. J Invest Dermatol 
123, 603-6. 

Further reading 

Bikowski J. (2001) The use of therapeutic moisturizers in various 
dermatologic disorders. Cutis 68 (Suppl), 3-11. 

Burgess CM. (2005) Cosmetic Dermatology. Berlin: Springer. 

Crowther JM, Sieg A, Blenkiron P, et al. (2008) Measuring the 
effects of topical moisturizers on changes in stratum corneum 
thickness, water gradients and hydration in vivo. Br J Dermatol 
159, 567-77. 

Del Rosso JQ. (2005) The role of the vehicle in combination acne 
therapy. Cutis 76 (Suppl), 15-8. 


Fisher GJ, Datta SC, Talwar HS, etal. (1996) Molecular basis of sun- 
induced premature skin ageing and retinoid antagonism. Nature 
379, 335-9. 

Fisher GJ, Varani J, Voorhees JJ. (2008) Looking older: fibroblast 
collapse and therapeutic implications. Arch Dermatol 144, 
666-72. 

Fisher GJ, Voorhees JJ. (1996) Molecular mechanisms of retinoid 
actions in skin. FASEB J 10, 1002-13. 

Fisher GJ, Wang ZQ, Datta SC, et al. (1997) Pathophysiology of 
premature skin aging induced by ultraviolet light. N Engl J Med 
337, 1419-28. 

Fluhr J. (2005) Bioengineering of the Skin: Water and Stratum Corneum , 
2nd edn. Boca Raton: CRC Press. 

Friedmann PS. (1986) The skin as a permeability barrier. In: Thody 
AJ, Friedmann PS, eds. Scientific Basis of Dermatology. Edinburgh, 
London: Churchill Livingstone, pp. 26-35. 

Held E, Jorgensen LL. (1999) The combined use of moisturizers and 
occlusive gloves: an experimental study. Am J Contact Dermatol 10, 
146-52. 

Jungermann E, Norman O, Sonntag V. (1991) Glycerin: A Key 
Cosmetic Ingredient. Vol. 11, Cosmetic Science and Technology Series. 
New York: Marcel Dekker. 

Kafi R, Kwak HS, Schumacher WE, et al. (2007) Improvement of 
naturally aged skin with vitamin A (retinol). Arch Dermatol 143, 
606-12. 

Loden M, Maibach HI. (1999) Dry Skin and Moisturizers: Chemistry and 
Function. Boca Raton: CRC Press. 

OrthDS. (1993) Handbook of Cosmetic Microbiology . New York: Marcel 
Dekker. 

Page-McCaw A, Ewald AJ, Werb Z. (2007) Matrix metalloprotein- 
ases and the regulation of tissue remodeling. Nat Rev Mol Cell Biol 
8 , 221-33. 

Rattan SI. (2006) Theories of biological aging: genes, proteins, and 
free radicals. Free Radio Res 40, 1230-8. 

Streicher JJ, Culverhouse WC Jr, Dulberg MS, etal. (2004) Modeling 
the anatomical distribution of sunlights. Photochem Photobiol 79, 
40-7. 

Verdier-Sevrain S, Bonte F. (2007) Skin hydration: a review on its 
molecular mechanisms. J Cosmet Dermatol 6, 75-82. 


129 


Chapter 17: Hand and foot moisturizers 

Teresa M. Weber 1 , Andrea M. Schoelermann 2 , Ute Breitenbach 2 , 
Ulrich Scherdin 2 , and Alexandra Kowcz 1 

^eiersdorf Inc, Wilton, CT, USA 
2 Beiersdorf AG, Hamburg, Germany 


BASIC CONCEPTS 

• Xerosis of the hands and feet is common, caused by a paucity of sebaceous glands. 

• Moisturization of the hands and feet can prevent eczematous disease and aid in disease eradication. 

• Effective moisturizers provide occlusive lipophilic substances that act as protectants and barrier replenishes, as well as 
hydrophilic agents that function as humectants to bind and hold water. 

• Recent recognition of the role of aquaporins, special moisture regulating channels, in skin cells has provided the opportunity for 
a new moisturization technology, focusing on substances that stimulate and operate through aquaporins. 


Introduction 

The hands and feet are prone to dryness and impaired 
barrier function because of their unique functional roles, 
predisposing the skin to heightened irritant sensitivity and 
the development of dermatoses. Protective and regenerative 
moisturizing skin care is the foundation for averting and 
treating dry skin associated skin diseases and disorders. 

Effective moisturizers provide occlusive lipophilic sub¬ 
stances that act as protectants and barrier replenishers, as 
well as hydrophilic agents that function as humectants to 
bind and hold water. The importance of urea as a physiologic 
humectant and natural moisturizing factor is discussed. 
Application of moisturizers containing urea is shown to 
increase its concentration and exert ultrastuctural changes 
in the stratum corneum, hydrate severely compromised 
skin, and support and enhance barrier function. In addition, 
the role of aquaporins and the underlying mechanisms of 
moisture homeostasis of the skin are discussed vis-a-vis new 
opportunities to create better actives and product formula¬ 
tions which can help regulate moisturization from within 
the skin. 


Moisturization needs of the hand and foot 

Skin of the hands and feet is different from other body sites. 
In particular, skin on the palms and soles is thicker, and has 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


a high density of eccrine sweat glands; however, it lacks 
apocrine glands. These sites are highly innervated and 
involved in most of the daily activities of life. Repetitive use 
of the hands and feet accompanied by pressure and friction 
can promote the formation of areas of thickened keratinized 
skin or calluses, which can crack and fissure. Site-specific 
requirements for hygienic care and diseases common to 
these sites have been described [!]• In addition, the hands 
and feet have special skincare needs for efficacious moisturi¬ 
zation as well as unique requirements for formulations that 
are compatible with their special sensory and functional 
roles and needs. 

Hand skin is particularly susceptible to xerosis and derma¬ 
titis. Constant use of the hands, frequent washing, and envi¬ 
ronmental, chemical, and irritant exposure can provoke 
these problems. Further, because the hands are especially 
prone to injury and exposed to irritants and pathogens, 
specific protectant skincare formulations can be highly ben¬ 
eficial to prevent irritation or occupational dermatoses such 
as hand eczema [2]. 

While the feet may be less likely to suffer from deleterious 
occupational exposures, environmental factors can have an 
impact on the moisture status of the foot skin. Cold, dry 
weather in winter, bare feet in summer, and the confine¬ 
ment of shoes can compromise the hydration state. Occlusive 
shoes and socks can also trap moisture and render the foot 
susceptible to microbial infections, especially from fungus, 
damaging the barrier function and dehydrating the skin. In 
addition, certain metabolic diseases can impact circulation 
and innervation of the extremities, which in turn affects skin 
hydration. In particular, reduced circulation and eccrine 
sweat gland activity in diabetics cause severe xerosis which 
can spiral into other severe foot problems. 


130 







17. Hand and foot moisturizers 


Protective and regenerative moisturizing skin care is the 
foundation for treating all dry skin associated skin diseases 
and disorders. While the underlying cause of dry skin in any 
specific skin disorder needs to be addressed, frequently the 
symptomatic control of severe xerosis by appropriate mois¬ 
turizers may reduce the need for more potent treatments, 
such as prolonged use of topical steroids and immune modu¬ 
lators, which can have detrimental side effects. 

Moisturizing creams containing urea have been reported 
to improve the physical and chemical nature of the skin 
surface, with the manifest benefits of smoothing, softening, 
and making dry skin more pliable [2]. Traditional moistur¬ 
izing emulsions have utilized non-physiologic emollients, 
humectants, and skin protectants to rehydrate the skin and 
reduce moisture loss. The identification and understanding 
of the structure and function of the stratum corneum barrier 
lipids and the role of water binding physiologic substances 
collectively referred to as natural moisturizing factors (NMF) 
led to the development of formulations enriched in these 
actives. Recent recognition of the role of aquaporins, special 
moisture regulating channels, in skin cells has provided the 
opportunity for a new moisturization technology, focusing 
on substances that stimulate and operate through 
aquaporins. 


Moisturizing formulations 
and technologies 

For thousands of years oils, animal and vegetable fats, waxes 
and butters have been used to moisturize the skin. 
Recognized for their emollient or skin smoothing and sof¬ 
tening properties, these substances were used to help restore 
dry skin to a more normal moisture balance. The first sig¬ 
nificant advancement from these simple moisturizers 
occurred over a hundred years ago when emulsifiers were 
developed to create the first stable water-in-oil emulsion [3]. 

A simple emulsion can be defined as a heterogeneous 
system that contains very small droplets of an immiscible (or 
slightly miscible) liquid dispersed in another type of liquid. 
These emulsions consist of a hydrophilic (water loving) and 
a lipophilic (oil loving) portion, either of which can make 
up the external or internal phases of the emulsion system. 
The external phase generally comprises the majority of the 
emulsion while the smaller internal phase consists of the 
dispersed droplets. Most commonly used moisturizer formu¬ 
lations are either oil-in-water (O/W) emulsion systems, 
where aqueous components predominate, or water-in-oil 
(W/O), where the majority of ingredients are non- 
aqueous. 

Emulsifiers are necessary components of emulsion systems 
as water-soluble and oil-soluble ingredients are not miscible. 
Emulsifiers are surface active agents that reduce the inter¬ 


facial tension between the two incompatible phases to create 
stable emulsion systems. The properties of the chosen emul¬ 
sifiers determine the final emulsion type. 

Major progress in recent decades has enabled the formula¬ 
tion of increasingly complex emulsions (e.g. water-in-oil-in- 
water emulsions, multilamellar emulsions), which combine 
and stabilize many incompatible ingredients for moisturizing 
products with unique delivery characteristics that are both 
highly effective and esthetically pleasing [4,3]. However, it 
is beyond the scope of this chapter to discuss the multitude 
of emulsion technologies which have been developed since 
the advent of the simple W/O system [6]. 

Occlusive materials and humectants are two major classes 
of moisturizing ingredients in many current moisturizers 
(Table 17.1). Occlusive materials coat the stratum corneum 
to inhibit transepidermal water loss (TEWL). Additionally, 
cholesterol, ceramides, and some essential and non-essential 
free fatty acids present in oils can help to replenish the 
natural lamellar barrier lipids that surround the squames in 
the stratum corneum, fortifying the barrier function of the 
skin. Some common examples of occlusive materials are 
petrolatum, olive oil, mineral oil, soybean oil, lanolin, 
beeswax, and jojoba oil. Petrolatum, lanolin, and mineral oil 
are considered occlusive materials, yet they also serve as 
emollients on the skin [7,8]. 

Humectants are materials that are capable of absorbing 
high amounts of water from the atmosphere and from the 
epidermis, drawing water into the stratum corneum for a 
smoother skin feel and look. Examples of well-known 
humectants include glycerin (or glycerol), sorbitol, urea, 
sodium hyaluronate, and propylene glycol. Glycerin is a 
widely used humectant with strong water binding 
capacity and holding ability, making it ideal for dry skin 
moisturizing formulations. Because of its importance in 
moisturizing products, it has been extensively reviewed 
elsewhere [9,10]. 

A number of commercially available hand and foot mois¬ 
turizers incorporate combinations of both humectants and 
occlusive materials to deliver the optimal skin benefits 
(Table 17.2). 


Natural moisturizing factors 

The NMF are a collection of hygroscopic substances in the 
skin that act synergistically to confer effective water binding 
properties. The NMF has been reported to be composed of 
approximately 40% amino acids, 12% pyrrolidone carboxy¬ 
lic acid, 12% lactates, 7% urea, 18% minerals, and other 
sugars, organic acids, citrates, and peptides [11]. These sub¬ 
stances, derived from eccrine sweat, extracellular compo¬ 
nents, largely from breakdown products of the insoluble 
protein filaggrin, have an important role in maintaining 


131 




HYGIENE PRODUCTS Moisturizers 


Table 17.1 Key classes of commonly used moisturizing ingredients. 


Key classes 

Moisturizing ingredients 

Function in skin 

Occlusives 

Petrolatum 

Moisturization by occlusion of the 


Waxes 

stratum corneum and/or replenishment 


Lanolin 

Mineral oil 

Cholesterol 

Ceramides 

Triglycerides and free fatty acids 
Sunflower oil 

Soybean oil 

Jojoba oil 

Olive oil 

Evening primrose oil 

Borage oil 

of lamellar barrier lipids 

Humectants 

Glycerin/glycerol 

Draws water from the formulation base, 


Sorbitol 

atmosphere, and from the underlying 


Sodium hyaluronate 

Propylene glycol 

epidermis to increase skin hydration 


Amino acids* 

*Natural moisturizing factors - absorb 


Lactate* 

large amount of water even in 


Pyrrolidone carboxylic acid* 

relatively low humidities. Provide 


Urea* 

aqueous environment for key 


Salts* 

enzymatic functions in the skin 





Table 17.2 Examples of commercially available hand and foot creams. 


Key ingredients 

Functions and claims 




Hand cream 

Foot cream 

1 

Glycolic acid, mineral oil, petrolatum 

Exfoliation and moisturization by 
"occlusives" to both smooth and soften skin 

Exfoliation and moisturization by 
"occlusives" to both smooth and 

soften skin 

II 

Glycerin, shea butter, almond oil, 
olive oil 

Moisturization of hands and softening of 
cuticles 

Moisturizes, soothes, and protects dry, 
cracked, and callused heels 

III 

Caprylic/capric triglycerides, glycerin, 
sunflower oil, olive oil, almond oil 

Moisturization of hands, nails, and cuticles 

Soothes and heals severely dry, 
cracked heels 

IV 

Beeswax, sweet almond oil 

Moisturizes and softens dry skin 

Prevents and heals cracked heels, 
calluses, corns, blisters 

V 

Lanolin, allantoin, glycerin, 
sunscreens: avobenzone, octinoxate 

Moisturizes skin and helps treat the signs of 
aging 


VI 

Glycerin, petrolatum, dimethicone, 
mineral oil 

Helps form a protective moisture barrier; 
heals and protects dry hands with 24-hour 
moisturization 


VII 

Urea, sodium lactate, glycerin 

Gently exfoliates and moisturizes; relieves 
dry skin associated with hand eczema 

Intensively moisturizes, smoothes and 
heals dry, cracked feet 

VIII 

Prescription urea (25%, 30%, 40%, 
or 50%), mineral oil, petrolatum 

Healing and debriding of hyperkeratotic skin 
and nails 

Healing and debriding of 
hyperkeratotic skin and nails 


132 









17. Hand and foot moisturizers 


(a) 


moisture in the non-viable layers of the epidermis. Because 
of the moisture gradient that exists from the well-hydrated 
dermis to the relatively moisture-deprived stratum corneum, 
the cutaneous moisturization state is a function of the occlu¬ 
sive barrier lipids in the stratum corneum and the humect - 
ant properties of the NMF [12]. Both are critical to retain 
moisture and resist TEWL and the dehydrating effects of the 
environment. Therefore, qualitative or quantitative changes 
in either the barrier lipids or the NMF components can alter 
skin hydration. 

Urea is a major constituent of the water-soluble fraction 
of the stratum corneum [13]. Because of the high water 
binding capacity of urea, the water content in the skin 
depends on its concentration. In dry skin and in keratiniza- 
tion disorders, a deficit of urea is often found in the stratum 
corneum, confirming its importance in skin moisture 
balance. The concentration of urea has been reported to be 
reduced by approximately 30% in clinically dry skin com¬ 
pared to healthy skin [14,13]. The stratum corneum of unaf¬ 
fected psoriatic skin reveals no deficit in urea content, but 
levels in psoriatic lesions are reduced by 40% [16]. However, 
in patients with atopic dermatitis there is a deficit of about 
70% in unaffected skin and about 85% in involved skin 
[17]. Urea has been demonstrated to be an effective moistur¬ 
izer for a range of dry skin conditions [18] and especially 
xerosis of the elderly [19,20]. Loden has recently compiled 
a summary of clinical data on the treatment of diseased skin 
with urea-containing formulations [21]. Besides improve¬ 
ments in skin hydration, urea may be enhancing the levels 
of linoleic acid and ceramides [22], providing an additional 
skin benefit. 

Urea is very soluble in water, but practically insoluble in 
lipids and lipid solvents. By its hydrogen-bond breaking 
effect, urea may expose water binding sites on keratin allow¬ 
ing the transport of water molecules into the stratum 


corneum, thereby leading to a plasticizing effect [23]. In 
addition, urea has proteolytic and keratolytic effects in con¬ 
centrations above 10% [21]. These activities are exploited 
in prescription formulations of 12-50%, which are often 
employed for debriding purposes in keratinization 
disorders. 

Lactic acid and salts of lactic acid, other efficacious 
components of the NMF, have also been used to treat dry 
skin conditions [11]. Like urea, the principal moisturizing 
effect is brought about by their humectancy. However, 
additional benefits of barrier support and restoration may 
be attributed to these NMF as an increase in ceramide 
synthesis in keratinocytes treated with lactic acid has been 
reported [24]. 


Ultrastructural effects 

Differential changes in skin hydration state and ultrastruc- 
ture after the application of various moisturizing products 
can be observed using scanning electron microscopy (SEM) 
of frozen sections from skin biopsies [25]. Figure 17.1 depicts 
the epidermis of skin treated with a commercial lotion with 
10% urea, sodium lactate, and glycerin (right), or treated 
with a vehicle lotion without urea, sodium lactate, and 
glycerin (left). From the SEM images it could be concluded 
that the product penetrated the entire stratum corneum, 
resulting in a more compact stratum corneum layer, with a 
20-40% reduction in corneocyte thickness. When compared 
with an untreated control (not shown), the vehicle treat¬ 
ment did not have an influence on the stratum corneum 
thickness. The compaction of the stratum corneum by the 
urea product suggests an improved barrier function which 
has been confirmed in other clinical studies demonstrating 
a reduction in TEWL [22]. 



Figure 17.1 Freeze-fracture scanning electron micrographs of the stratum corneum of skin treated with a vehicle lotion (a) or the vehicle lotion 
containing 10% urea and sodium lactate (b). 


133 






hygiene PRODUCTS Moisturizers 


Clinical demonstrations of product efficacy 
of sodium lactate and urea formulations 

Hand care 

Several clinical studies were conducted to evaluate the 
ability of a fragrance-free, O/W emulsion containing 5% 
urea and 2.5% sodium lactate to fortify the skin of healthy 
subjects, and to moisturize, protect, and treat others with 
compromised hand skin. 

Improvements in urea content 

Thirty-one volunteers with healthy skin were enrolled in 
this study. Subjects refrained from the use of topical treat¬ 
ments for a period of 1 week and then applied the test 
product twice daily for 2 weeks. Urea content of the skin, 
moisturization state, and skin roughness were assessed at 
baseline, after 2 weeks of treatment, and 3 days after the 
last application. A significant increase (p < 0.05) in the urea 
content of the skin compared with untreated skin was 
observed (Figure 17.2) as well as significant improvements 
in skin hydration levels and roughness (data not shown). 
Franz cell porcine skin penetration studies confirmed the 


1600 “i 



Baseline 2 weeks 3 days 
regression 

Length of treatment 

^Significant difference relative to untreated, p < 0.05 

Figure 17.2 Stratum corneum urea content before application, after 2 
weeks of daily use, and 3 days after discontinuing application of an 
oil-in-water emulsion containing 5% urea and 2.5% sodium lactate. 


Table 17.3 Mean clinical grading scores at baseline and after 4 
weeks of daily use of a 5% urea and sodium lactate oil-in-water 
emulsion. 



Cracking/fissuring 

Dryness/scaling 

Eczema severity 

Baseline 

4.78 

6.61 

3.04 

Week 4 

2.91* 

3.59* 

1.66* 


* Significant difference relative to baseline, p < 0.05. 


penetration and distribution of urea throughout the skin 
compartments 24 hours after application of a 5% urea body 
cream formulation: 54% stratum corneum, 7% in the viable 
epidermis, 22% in the dermis, and 17% in the receptor 
phase. 

Improvement in eczema and xerosis 

In a second 4-week controlled usage study, 23 subjects with 
hand eczema and 14 subjects with hand dermatitis/xerosis 
were enrolled. The subjects applied the test cream at least 
twice per day (morning and evening), and as often as 
needed. Clinical evaluations were made at baseline, and 
after 2 and 4 weeks of hand cream use for cracking/fissuring 
and dryness/scaling (0-8 scale), and erythema, edema, 
burning, stinging, and itching (0-3 scale). Subjects with 
eczema were also evaluated using an Investigator's Global 
Assessment for Eczema (0-5 scale). Digital photographs 
were taken at each of the clinical visits. 

Significant improvements (p < 0.05) in clinical grading 
scores at week 4 relative to baseline were observed for 
dryness/scaling and cracking/fissuring, and the Investigators 
Global Assessment for Eczema (Table 17.3). Average irrita¬ 
tion scores were also significantly reduced and negligible by 
week 4 for itching, stinging, and burning (data not shown). 

Digital photographs captured the dry, compromised hand 
skin condition at the baseline visit, and demonstrated 
improvements that reflected the clinical assessments. Figure 
17.3 shows the typical improvements observed in subjects 
at week 4 (right), compared with baseline (left). 

In conclusion, appropriate hand care can both treat and 
prevent common dermatoses such as hand eczema. 

Foot care 

Patients with diabetes mellitus can exhibit a number of 
cutaneous manifestations as a result of changes in metabolic 
status and/or circulatory and neural degeneration [26]. 
Management of dry skin in these individuals is important to 
preserve barrier integrity which can help prevent bacterial 
and fungal infections. In particular, the heel skin can be very 
dry and scaly, prone to forming cracks and fissures which 
can lead to wounds that have difficulty healing. 

A 6-week controlled usage study of a cream containing 
10% urea, 5% sodium lactate, and glycerin as a daily treat¬ 
ment for the feet was conducted in 31 type I and II diabetic 
patients. This patient population was chosen because of their 
highly compromised foot skin condition. The subjects' heels 
were evaluated for roughness, scaling and cracking, and 
subjective irritation was also documented. Color photo¬ 
graphs of the heels, taken before and after 6 weeks of treat¬ 
ment, documented the marked improvement in heel skin 
condition (Figure 17.4). In addition, significant reduction of 
roughness, scaling, and cracking was observed. In spite of 
the severely compromised skin condition at baseline, only 
one patient reported a mild irritation on the application site 


134 











17. Hand and foot moisturizers 



Figure 17.3 Improvement in hand eczema (top) and xerosis (bottom) after 4 weeks of daily usage (right) of a hand cream containing 5% urea and 
sodium lactate. 


which did not interfere with his completing the study 
according to the protocol. 

A second multicenter study of 604 patients with dry or 
severely dry, chapped feet and generalized xerosis (258, 
42.7%), diabetes (179, 29.6%) or atopic dermatitis (113, 
18.7%) was conducted in Germany and Austria. The patients 
applied a foot cream containing 10% urea, 5% sodium 
lactate, and glycerin at least twice daily for 2 weeks. While 
319 patients used specific foot treatment products to care for 
their feet at the baseline visit, only 20 used other topical 
products in addition to the foot cream during the study 
period. The foot skin was clinically graded for xerosis, 
scaling, and cracking at baseline and after 2 weeks of treat¬ 
ment on a 5-point scale (none, slight, moderate, severe, or 
very severe). Table 17.4 documents the improvement in skin 
condition after 2 weeks of foot cream usage, showing sig¬ 
nificant and marked decreases in the percentage of patients 
with severe or very severe symptoms, and overall noticeable 
improvements in 95% of the patients. In this large patient 
population, the investigating dermatologists judged the tol¬ 
erability to be very good or good in 96.7% of the patients, 
recommending continued product use. 


These data and many other published studies [18-22] 
support the therapeutic value and excellent safety profile of 
urea when administered topically to treat various dry skin 
conditions. 


The future: Next-generation moisturizers 

Water homeostasis of the epidermis is important for the 
appearance and physical properties of skin, as well as for the 
water balance of the body. Skin moisture balance depends 
on multiple factors including external humidity, uptake of 
water into the epidermis, skin barrier quality, and endog¬ 
enous water binding substances. Biosynthesis and degrada¬ 
tion of skin components is also influenced by water balance, 
impacting the moisturization state of the epidermal layers. 
In recent times, aquaporins (AQP), important hydration¬ 
regulating elements in the lower epidermis, have been 
described [27]. 

The first indications of the critical importance of AQP in 
regulating tissue hydration came from investigations of 


135 


















HYGIENE PRODUCTS Moisturizers 



Figure 17.4 Improvement in diabetic foot skin after 6 weeks of daily usage of a foot cream containing 10% urea and 5% sodium lactate. 
Pretreatment photos (left) of two different subjects (top and bottom) and their corresponding week 6 photos (right). 


Table 17.4 Clinical grading scores before and after 2 weeks of 
treatment. Percentage of patients with none or slight and severe or 
very severe symptoms (100% = 604 patients). 




None or 
slight (%) 

Severe or very 
severe (%) 

Xerosis 

Baseline 

5 

67 


Week 2 

69 

6 

Scaling 

Baseline 

22 

44 


Week 2 

79 

6 

Cracking 

Baseline 

26 

32 


Week 2 

66 

8 


other organ systems, in particular the kidney [28]. Since 
their initial discovery, AQP genes have been cloned and, to 
date, 13 different genes (AQP 1-13) have been identified 
[29]. The first proof for their relevance in skin came from 
Ma et al. [30] who produced knockout mice lacking AQP3, 
which exhibited a reduced stratum corneum hydration. 
Studies confirmed the importance of these findings in dry 
human skin. Subjects whose epidermal barriers were 
damaged by a week-long tenside-based treatment that 


resulted in dry, compromised skin, showed a significant 
decrease in the number of AQP3 pores (p = 0.04). The pores 
were quantified by analysis of Western blots, and a 43% 
reduction in the dry skin samples was observed. 

Further, in other skin conditions associated with skin 
dryness, a reduction in AQP3 has also been observed. 
Specifically, an age-related decline in AQP3 levels, as well 
as decreases associated with chronic sun exposure were 
reported [31]. 

Water and the moisturizing substances glycerol and urea 
have been found to be transported through the AQP in skin, 
providing moisture from within to the epidermis [32]. 
Expanding knowledge on the activity and regulation of 
AQP3 has led to the pursuit of a new class of actives that 
can modulate the expression of these water channels. 

Enhanced glycerol derivatives 

In vitro studies on human keratinocytes demonstrated a sig¬ 
nificant increase in AQP3 levels by a specific enhanced glyc¬ 
erol derivative (EGD), designed and synthesized to confer 
specific structural and osmotic properties. Figure 17.3 depicts 
the enhanced AQP3 levels of EGD treated human keratino¬ 
cytes after 48 hours of incubation. 

Additional in vitro studies measuring AQP3 mRNA levels 
in human keratinocytes confirmed these findings. In con¬ 
trast to glycerol treatment, EGD increased mRNA expres- 


136 








17. Hand and foot moisturizers 


DAPI ■ AQP3/DAPI ■ AQP3/DAPI 


background 10 m ' untreated EGD treated 


Figure 17.5 Immunohistochemical localization of the AQP3 protein in keratinocyte monolayers stained with a rabbit antihuman AQP3 antibody. 
Background control (left), untreated control (center), treatment with 3% enhanced glycerol derivative for 48 hours (right). 


J 

Vehicle + Vehicle+ 

glycerol glycerol+ 

EGD 

^Significantly different, p < 0.05. 

Figure 17.6 In vivo study of 23 volunteers with dry skin. 

Transepidermal water loss (TEWL) measurement after the following 
treatments: vehicle; vehicle with 6.5% glycerol; and vehicle with 6.5% 
glycerol and 5% enhanced glycerol derivative (EGD). 

sion relative to the control. Further, to assess the efficacy of 
this new active, in vivo placebo-controlled studies were con¬ 
ducted. Figure 17.6 demonstrates the results of a study of 
23 subjects, whose epidermal barriers were damaged by a 
tenside-based treatment, resulting in dry, compromised 
skin. The restoration of the epidermal barrier was assessed 
weekly by measuring TEWL on treated skin sites. The 
applied topical test lotions included a vehicle preparation, 
vehicle plus 6.5% glycerol, and the vehicle with 6.5% glyc¬ 
erol and 5% EGD. 

After damaging the skin's barrier for 1 week, vehicle treat¬ 
ment was ineffective at restoring the barrier to baseline 
levels, exhibiting greater moisture loss levels in the skin. 
Treatment with the glycerol-containing vehicle showed a 
reduction of the TEWL compared with the vehicle. However, 
a superior and significant barrier restoration and fortification 
is observed with the glycerol-EGD containing formulation 
compared with both vehicle and vehicle with glycerol. 


Conclusions 

Moisturizing substances have been used for thousands of 
years to improve the condition of compromised skin. The 
advent of stable emulsions and subsequent advancements in 
emulsion technologies provided improved elegance and effi¬ 
cacy for moisturizing products. More than 100 years of 
process refinements, discovery of new ingredients, and the 
growing understanding of the NMF and biologic mecha¬ 
nisms that regulate the skin's moisture balance have con¬ 
tributed toward products with greatly enhanced stability, 
esthetics, and efficacy. In contrast to ingredients that exert 
their effects solely from the surface of the skin, the recent 
discovery and understanding of the function of AQP and 
new appreciation of the underlying mechanisms of moisture 
homeostasis of the skin provides new opportunities to create 
even better actives and product formulations which can help 
regulate moisturization from within the skin. 

References 

1 Draelos ZD. (2006) Cutaneous formulation issues. In: Draelos Z, 
Thamen L, eds. Cosmetic Formulation of Skin Care Products. New 
York: Taylor & Francis, pp. 3-34. 

2 Zhai H, Maibach HI. (1998) Moisturizers in preventing irritant 
contact dermatitis: an overview. Contact Dermatitis 38, 241-4. 

3 Lifschiitz I. (1906) Verfahren zur Herstellung stark wasserauf- 
nahmefahiger Salbengrundlagen. Patent DE 167849. 

4 Fluhr JW, Darlenski R, Surber C. (2008) Glycerol and the skin: 
holistic approach to its origin and functions. Br J Dermatol 159, 
23-34. 

5 Epstein H. (2006) Skin care products. In: Paye M, Barel A, 
Maibach H, eds. Handbook of Cosmetic Science and Technology , 2nd 
edn. Boca Raton: CRC Press, pp. 427-39. 

6 Schneider G, Gohla S, Kaden W, et al. (1993) Skin cosmetics. In: 
Uhlmann's Encyclopedia of Industrial Chemistry. Weinheim: VCH 
Verlagsgesellschaft, pp. 219-43. 

7 Rajka G. (1995) Atopic dermatitis. In: Baran R, Maibach H, eds. 
Cosmetic Dermatology. London: Martin Dunitz, pp. 253-8. 


110 “| 



Vehicle 



137 











HYGIENE PRODUCTS Moisturizers 


8 Draelos ZD. (2005) Dry skin. In: Draelos ZD, ed. Cosmeceuticals. 
Philadelphia: Elsevier Saunders, pp. 167-8. 

9 Zocchi G. (2006) Skin feel agents. In: Paye M, Barrel A, Maibach 
H, eds. Handbook of Cosmetic Science and Technology , 2nd edn. Boca 
Raton: CRC Press, pp. 247-64. 

10 Sagiv A, Dikstein S, Ingber A. (2001) The efficiency of humec- 
tants as skin moisturizers in the presence of oil. Skin Res Technol 
7, 32-8. 

11 Harding CR, Rawlings AV. (2006) Effects of natural moisturizing 
factor and lactic acid isomers on skin function. In: Maibach HI, 
Loden M, eds. Dry Skin and Moisturizers: Chemistry and Function , 
2nd edn. Boca Raton: CRC Press LLC, pp. 187-209. 

12 Rawlings AV, Harding CR. (2004) Moisturization and skin barrier 
function. Dermatol Ther 17, 43-8. 

13 Swanbeck G. (1992) Urea in the treatment of dry skin. Acta Derm 
Venereol 177, 7-8. 

14 Mueller KH, Pflugshaupt C. (1979) Urea in dermatology I. 
ZblHaut 142, 157-68. 

15 Mueller KH, Pflugshaupt C. (1982) Urea in dermatology II. 
ZblHaut 167, 85-90. 

16 Proksch E. (1994) Harnstoff in der Dermatologie. Dtsch Med 
Wochenschr 119, 1126-30. 

17 Wellner K, Wohlrab W. (1993) Quantitative evaluation of urea 
in stratum corneum of human skin. Arch Dermatol Res 285, 
239-40. 

18 Scholermann A, Filbry A, Rippke F. (2002) 10% urea: an effec¬ 
tive moisturizer in various dry skin conditions. Ann Dermatol 
Venereol 129, 1S422, P0259. 

19 Schoelermann A, Banke-Bochita J, Bohnsack K, et al. (1998) 
Efficacy and safety of Eucerin® 10% urea lotion in the treat¬ 
ment of symptoms of aged skin. J Dermatolog Treat 9, 175-9. 

20 Norman RA. (2003) Xerosis and pruritus in the elderly: recogni¬ 
tion and management. Dermatol Ther 16, 254-9. 

21 Loden M. (2006) Clinical evidence for the use of urea. In: 
Loden M, Maibach HI, eds. Dry Skin and Moisturizers. Chemistry 


and Function , 2nd edn. Boca Raton: Taylor & Francis, pp. 
211-25. 

22 Pigatto PD, Bigardi AS, Cannistraci C, Picardo M. (1996) 10% 
urea cream (Eucerin) for atopic dermatitis: a clinical and labora¬ 
tory evaluation. J Dermatolog Treat 7, 171-6. 

23 McCallion R, Wan Po AL. (1993) Dry and photo-aged skin: 
manifestations and management. J Clin Pharm Ther 18, 
15-32. 

24 Rawlings AV, Davies A, Carlomusto M, et al. (1995) Effect of 
lactic acid isomers on keratinocyte ceramide systhesis, stratum 
corneum lipid levels and stratum corneum barrier function. Arch 
Dermatol Res 288, 383-90. 

25 Richter T, Peuckert C, Sattler M, et al. (2004) Dead but highly 
dynamic: the stratum corneum is divided into three hydration 
zones. Skin Pharmacol Physiol 17, 246-57. 

26 Nikkels-Tassoudji N, Henry F, Letawe C, etal. (1996) Mechanical 
properties of the diabetic waxy skin. Dermatology 192, 19-22. 

27 Hara-Chikuma M, Verkman AS. (2008) Roles of aquaporin-3 in 
the epidermis. J Invest Dermatol 128, 2145-51. 

28 Agre P. (2006) Aquaporin water channels: from atomic struc¬ 
ture to clinical medicine. Nanomedicine: Nanotechnology, Biology 
and Medicine 2, 266-7. 

29 Verkman AS. (2008) Mammalian aquaporins: diverse physio¬ 
logical roles and potential clinical significance. J Exp Med 10, 
1-18. 

30 Ma T, Hara M, Sougrat R, etal. (2002) Impaired stratum corneum 
hydration in mice lacking epidermal water channel aquaporin-3. 
J Biol Chem 27, 17147-53. 

31 Dumas M, Sadick NS, Noblesse E, et al. (2007) Hydrating skin 
by stimulating biosynthesis of aquaporins. J Drugs Dermatol 6 
(Suppl), 20-4. 

32 Hara M, Verkman AS. (2003) Glycerol replacement corrects 
defective skin hydration, elasticity, and barrier function in 
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7360-5. 


138 


Chapter 18: Sunless tanning products 

Angelike Galdi, Peter Foltis, and Christian Oresajo 

L'Oreal Research, Clark, NJ, USA 


BASIC CONCEPTS 

• Tanned skin is considered attractive among fair-skinned individuals. 

• Self-tanning preparations containing dihydroxyacetone (DHA) induce a temporary safe staining of the skin simulating 
sun-induced tanning. 

• Self-tanners are formulated into sprays, lotions, creams, gels, mousses, and cosmetic wipes. 

• The tanning effect of DHA begins in the deeper part of the stratum corneum before expanding over the entire stratum 
corneum and stratum granulosum resulting in the production of brown melanoidins. 

• DHA products do not confer photoprotection unless sunscreen filters are added to the formulation. 


Introduction 

Social norms for tanning in the USA have dramatically 
changed in recent times. The presence of a tanned body at 
one time conveyed the social status of an outdoor laborer. 
Now, having a tan, especially during the winter months, 
indicates affluence. 

More information has become available regarding the del¬ 
eterious effects of UV exposure. [1-3]. The public is begin¬ 
ning to understand the dangers, thereby modifying their 
lifestyle choices towards safer practices. However, the change 
has been slow because sun exposure behavior is in part 
influenced by psychologic and societal factors [4-6]. Self¬ 
tanning preparations are becoming an increasingly impor¬ 
tant option for those desiring the tanned look but not 
exposing themselves to undue harm. 


Sunless tanning products 
Definition 

Self-tanning products, or sunless tanners, are preparations 
that when applied topically impart a temporary coloration 
to the skin mimicking skin color of naturally sun-tanned 
skin. Depending on the formulation and the active ingredi¬ 
ents, the onset of color formation can be anything from 
immediate to several hours and can last up to 1 week. 

Self-tanning formulations were introduced in the 1960s. 
Consumers' acceptability soon waned because of unattrac- 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


tive results such as orange hands, streaking, and poor colora¬ 
tion. Because of these drawbacks, consumers today still 
associate sunless tanning with these undesirable results. 
However, improved formulations have appeared on the 
market. Refinements in the dihydroxyacetone (DHA) man¬ 
ufacturing process has aided in the creation of formulations 
that produce a more natural-looking color and better 
longevity. 

Active ingredients 

The most widely used and most efficacious active ingredient 
in self-tanners is DHA. It is the only ingredient that is cur¬ 
rently recognized as a self-tanning agent by the US Food and 
Drug Administration (FDA) [7]. DHA-based sunless tanners 
have been recommended by the Skin Cancer Foundation, 
the American Academy of Dermatology Association, and the 
American Medical Association [8-10]. DHA is a triose and 
is the simplest of all ketoses (Figure 18.1). 

Mechanism of action of DHA 

Ketones and aldehydes react with primary amines to form 
Schiff bases [11]. This is similar to the Maillard reaction, also 
known as non-enzymatic browning, and involves, more 
specifically, the reaction between carbohydrates and primary 
amines [12]. 

DHA is able to penetrate into the epidermis because of its 
size. Pyruvic acid is formed from DHA and either can react 
with sterically unhindered terminal amino groups in the 
amino acids of epidermal proteins. The epsilon amino group 
of lysine and the guanido group of arginine are particularly 
susceptible to nucleophilic attack by the reactive carbonyl 
oxygen. Epidermal proteins contain high concentrations of 
both of these amino acids. Based on photoacoustic depth 
profilometry, the tanning effect of DHA begins in the deeper 


139 







hygiene PRODUCTS Moisturizers 


0 

ho^A^oh 

Figure 18.1 Chemical structure of dihydroxyacetone (DHA). 

part of the stratum corneum layer (15-22 pm) before expand¬ 
ing over the entire stratum corneum and stratum granulo- 
sum [13,14]. Subsequent steps of the reaction mechanism 
are not fully understood. The resultant products are brown 
in color and are collectively referred to as melanoidins. 

Alternate actives 

As previously stated, US federal regulations recognize only 
DHA as a sunless tanning agent [7]. Alternative technologies 
exist, however, with the capability to impart an artificial tan 
to the skin. 

Reducing sugars other than DHA can act as Maillard reac¬ 
tion intermediates and therefore have the potential for use 
as sunless tanning agents [15]. Reducing sugars, in basic 
solution, form some aldehyde or ketone. This allows the 
sugar to act as a reducing agent in the Maillard reaction of 
non-enzymatic browning. Reducing sugars include glucose, 
fructose, glyceraldehyde, lactose, arabinose, and maltose. 

Unfortunately, a large amount of heat energy is required 
to trigger the glycation reaction between glucose, the most 
commonly known reducing sugar, and free amines. Such 
properties render many reducing sugars useless for sunless 
tanning products. An exception is the keto-tetrose, erythu- 
lose. Although this reducing sugar produces a more gradual 
tan than DHA, it has been utilized as a self-tanning enhancer 
for years. 

As corporations continue to aggressively pursue new 
sunless tanning technologies, reducing sugars may provide 
the next generation of self-tanning actives. 


Formulation challenges 

The content of DHA in self-tanning products depends on the 
desired browning intensity on the skin and is normally used 
in the range 4-8%. Depending on the type of formulation 
and skin type, a tan appears on the skin about 2-3 hours 
after use. During product storage, the pH of a DHA- 
containing formulation will drift over time to about 3-4. At 
this pH, DHA is particularly stable. In order to ensure end 
product stability, certain key factors must be considered. 

pH and buffers 

The pH of DHA-containing formulation drops during storage. 
The resulting pH lies in the range of 3-4. In the past, buffer¬ 
ing was recommended to keep the pH at a level of 4-6. 


However, investigations have since shown that the storage 
stability of DHA could be increased when formulations are 
kept at a pH of 3-4 and buffering at a higher pH enhances 
the degradation of DHA [16]. The pH of a formulation may 
be adjusted to approximately 3-4 by using a small amount 
of citric acid or using acetate buffers as they do not affect 
DHA stability [17]. 

Processing and storage of DHA 

Storage and heating of DHA above 40 °C should be avoided 
as it causes rapid degradation. During manufacturing proc¬ 
esses that require heating (as in the case of emulsions), DHA 
should not be added until the formulation has been cooled 
down to below 40 °C. Additionally, finished products con¬ 
taining DHA should be sold in opaque, or other UV-protective 
packaging, as well as resealable packaging, to limit exposure 
to air. 

Nitrogen-containing compounds 

Amines and other nitrogen-containing compounds should 
be avoided in DHA-containing formulations. This includes 
collagen, urea derivatives, amino acids, and proteins. The 
reactivity of DHA towards these compounds can lead to its 
degradation, therefore resulting in the loss in efficacy and 
acceptability of resulting color. However, some commercial 
formulations combine DHA with nitrogen-containing con¬ 
taining compounds (e.g. amino acids). This combination 
provides a perceptual advantage to customers as provides 
within tanning 1 hour as a result of the accelerated reaction 
between DHA and amino acids. This tan is not substantive, 
however, and most of it is easily washed off [17]. 

Sunscreens 

A tan achieved with DHA alone does not offer sun protec¬ 
tion comparable to that of sunscreens. However, it is possible 
to combine DHA with sunscreens to achieve a product with 
sun protection. Inorganic sunscreens such as titanium 
dioxide, zinc oxide, and nitrogen-containing sunscreens 
should be avoided as they induce rapid degradation of DHA. 

As a final stability check, periodic determination of DHA 
dosage is recommended to ensure end product and long¬ 
term stability and efficacy. A simple high performance liquid 
chromatography (HPLC) method exists using an amine 
column with acetonitrile/water (75:25) as a mobile phase. 
Detection is at 270nm. 


Delivery vehicles 
Creams and lotions 

Self-tanning creams and lotions tend to be the most widely 
used of all of the self-tanning vehicles. Our studies have 
confirmed that although conventional, creams and lotions 
are preferred by consumers because of their ease of use and 


140 




18. Sunless tanning products 


reduced likelihood of having streaky color results. This is 
most likely because of the extended play time (e.g. rub-in 
time) offered by cream and lotion vehicles. 

In selecting the appropriate ingredients for formulation, 
the use of non-ionic emulsifiers is recommended over ionic 
emulsifiers because of improved stability of the DHA [16]. 
Additionally, xanthan gum and polyquaternium-10 may be 
used for thickening emulsions. 

Emollients have an important role in many self-tanning 
formulations as they impart hydration to the skin, play time 
during application, and a smooth and silky after feel. Types 
of emollients include oils, waxes, fatty alcohols, silicone 
materials, and certain esters. 

Emulsions with DHA are particularly susceptible to micro¬ 
bial attack. Parabens, phenoxyethanol, and mixtures thereof 
are recommended [16]. 

Gels and gelees 

Thickening formulations containing DHA, particularly to 
produce a clear gel, is relatively difficult because many of 
the conventional thickeners are not compatible with DHA. 
Studies have found that hydroxyethylcellulose, methylcel- 
lulose, and silica are good choices, whereas carbomers, 
PVM/MA decadiene crosspolymer, and magnesium alumi¬ 
num silicate are not acceptable as they cause rapid degrada¬ 
tion of DHA [16]. 

Silicones such as dimethicone and cyclomethicones have 
increased in popularity over recent years, particularly for 
producing water-in-silicone emulsions (typically classified as 
gelees). Gelees are similar in appearance to gels; however, 
they tend to offer improved play time and skin feel over gels 
as they contain high levels of the silicone emollients. 


Regulatory considerations 

The US FDA considers sunless tanning actives as color addi¬ 
tives as they impart color to the skin. According to 21CFR70, 
color additives are defined as: "A dye, pigment, or other 
substance...that, when added or applied to a food, drug or 
cosmetic or to the human body or any part thereof, is 
capable (alone or through reaction with another substance) 
of imparting a color thereto" [18]. 

The actives permitted in the sunless tanning products in 
the USA are limited to those approved for use as such. The 
following color additives appear in the Code of Federal 
Regulations in Tables 18.1 and 18.2. 

Labeling requirements are also specified under current 
FDA guidelines. All sunless tanning products that do not 
contain sun protection factor (SPF) protection must be 
labeled with the following warning statement (US Code of 
Federal Regulations): "Warning - This product does not 
contain a sunscreen and does not protect against sunburn. 
Repeated exposure of unprotected skin while tanning may 


Table 18.1 Color additives exempt from certification per 21CFR73 
2003 (US Code of Federal Regulations). 


Aluminum powder 

Copper powder 

Luminescent zinc 

Annatto 

Dihydroxyacetone 

Manganese violet 

(3-Carotene 

Disodium EDTA copper 

Mica 

Bismuth citrate 

Ferric ammonium 

Potassium sodium 

Bismuth oxychloride 

ferrocyanide 

copper 

Bronze powder 

Ferric ferrocyanide 

Pyrophyllite 

Caramel 

Guaiazulene 

Silver 

Carmine 

Guanine 

Sulfide 

Chromium oxide 

Henna 

Titanium dioxide 

greens 

Iron oxides 

Ultramarines 

Chlorophyllin 

Lead acetate 

Zinc oxide 


Table 18.2 Color additives per 21CFR73 2003 (US Code of Federal 
Regulations). 


Citrus Red No. 2 

D&C 

Red 

No. 17 

D&C Yellow No. 10 

D&C Blue No. 4 

D&C 

Red 

No. 21 

D&C Yellow No. 11 

D&C Blue No. 6 

D&C 

Red 

No. 22 

Ext. D&C Violet No. 2 

D&C Blue No. 9 

D&C 

Red 

No. 27 

Ext. D&C Yellow No. 7 

D&C Brown No. 1 

D&C 

Red 

No. 28 

FD&C Blue No. 1 

D&C Green No. 5 

D&C 

Red 

No. 30 

FD&C Blue No. 2 

D&C Green No. 6 

D&C 

Red 

No. 31 

FD&C Red No. 3 

D&C Green No. 8 

D&C 

Red 

No. 33 

FD&C Red No. 4 

D&C Orange No. 4 

D&C 

Red 

No. 34 

FD&C Red No. 40 

D&C Orange No. 5 

D&C 

Red 

No. 36 

FD&C Yellow No. 5 

D&C Orange No. 10 

D&C 

Red 

No. 39 

FD&C Yellow No. 6 

D&C Orange No. 11 

D&C 

Violet No. 2 

Orange B 

D&C Red No. 6 

D&C 

Yellow No. 7 

Phthalocyaninato2-Copper 

D&C Red No. 7 

D&C 

Yellow No. 8 



increase the risk of skin aging, skin cancer and other harmful 
effects to the skin even if you do not burn" [18]. 


Product attributes 

Coloration 

The onset of coloration starts at approximately 2-3 hours 
and will continue to darken for 24-72 hours after a single 
application, depending on formulation and skin type. 


141 









HYGIENE PRODUCTS Moisturizers 


Because DHA forms covalent bonds with epidermal proteins, 
the tan will not sweat off or wash away with soap or water. 
The color gradually fades over 3-10 days, in conjunction 
with stratum corneum exfoliation. Any product or process 
that increases the rate of cell turnover or removes portions 
of the stratum corneum will decrease the longevity of the 
color. Thus, preparations containing alpha- and beta- 
hydroxyacids and retinoids, as well as microdermabrasion 
creams and the process of shaving, decrease the longevity of 
coloration from self-tanning products. 

Evaluation 

Various spectrophotometric methods can be used to evalu¬ 
ate the coloration parameters of self-tanners such as onset 
of color and longevity of color. The most popular is the 
L*a*b* standard from Commission Internationale d'Eclairage 
(CIE). The three coordinates of CIELAB represent the light¬ 
ness of the color (L* = 0 yields black and L* = 100 indicates 
diffuse white), its position between red/magenta and green 
(a*, negative values indicate green while positive values 
indicate magenta), and its position between yellow and blue 
(b*, negative values indicate blue and positive values indi¬ 
cate yellow). The total color difference between any two 
colors in L*a*b* can be approximated by treating each color 
as a point in a three-dimensional space (with three compo¬ 
nents: L*, a*, b*) and taking the Euclidean distance between 
them (AE). AE is calculated as the square root of the sum of 
the squares of AL*, Aa* and Ab* [19]. It is generally recog¬ 
nized that 1.3 AE units is the minimal difference detectable 
to the eye. Comparisons to baseline readings can yield onset 
of tanning (usually readings at 30 minutes, 60 minutes, etc.) 
and longevity of tanning (readings at 48 hours, 72 hours, 
etc.). 

Moisturization 

The recent trend in cosmetic products is to be multifunc¬ 
tional. Moisturizing formulations are increasing in popular¬ 
ity in keeping with this trend. Formulations with 8-24 hour 
hydration claims are not uncommon. Current self-tanners 
are formulated into sprays, lotions, creams, gels, mousses, 
and cosmetic wipes. In general, there are no obstacles to 
obtaining satisfactory levels of hydration, although there are 
some compromises that may have to be made. Alcohol is 
often incorporated to achieve quick-drying formulations. 
The trade off is sacrificing some level of hydration. This can 
be offset with humectants such as glycerin or sodium 
hyaluronate. 


Trends in sunless tanning 

Daily use moisturizers/glow 

Face and body moisturizers with low levels of DHA have 
grown in popularity over the past 3 years. Although not new 


to the market, the concept of using a daily moisturizer that 
imparts gradual color was particularly well-received by the 
faint in heart who were afraid of making mistakes and/or 
turning orange with the use of traditional sunless tanners. 
Typically formulated with 1-3% DHA, glow moisturizers are 
easy to apply and, depending on the formulation and user's 
skin tone, may impart a darker shade to the skin after 1-3 
applications. 

No-rub mists 

No-rub sunless tanning mists have been sought out as the 
less expensive alternatives to the airbrushing trend. These 
multiangle applicator systems allow for simple, even, and 
often hands-free application. The formulation base systems 
are typically hydroalcoholic or aqueous solutions, therefore 
allowing for quick-drying properties. 

Sunless tanning products with UV protection 

The tan imparted by sunless tanners is not adequate to 
protect against UVB and UVA damage. Sunless tanners must 
therefore carry the required FDA warning statement [19]. 
Sunless tanning products that do contain sunscreen are 
growing in popularity because of their multifunctional 
properties. 


Conclusions 

With an increasing awareness of the harmful acute and 
chronic effects of UV damage, sunless tanning use remains 
a popular alternative to tan seekers. Modern day formula¬ 
tions are efficacious, well-tolerated, easy-to-use, and provide 
natural looking results. A probable increase in patient com¬ 
pliance of safe sun practices can therefore be anticipated. 

References 

1 Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. 
CA Cancer J Clin 56, 106-30. 

2 American Cancer Society. (2006) Cancer Facts and Figures 2006: 
American Cancer Society. 

3 Elwood JM (1993). Recent developments in melanoma epide¬ 
miology, 1993. Melanoma Res 3, 149-56. 

4 Garvin T, Wilson K. (1999) The use of storytelling for under¬ 
standing women's desires to tan: lessons from the field. 
Professional Geographer Vol. 51, 2, 297-306. 

5 Cokkinides V, Weinstock M, Glanz K, Albano J, Ward E, Thun 
M. (2006) Trends in sunburns, sun protection practices, and 
attitudes toward sun exposure protection and tanning among 
US adolescents, 1998-2004. Pediatrics 118, 853-64. 

6 Cokkinides V, Weinstock MA, O'Connell MC, Thun MJ. (2002) 
Use of indoor tanning sunlamps by US youth, ages 11-18 years, 
and by their parents or guardian caregivers: prevalence and cor¬ 
relates. Pediatrics 109, 1124-30. 

7 United States Code of Federal Regulations 21CFR 73.2150, 
2002 . 


142 




18. Sunless tanning products 


8 www.skincancer.org 

9 www.aad.org 

10 www.ama-assn.org 

11 Morrison RT, Boyd RN. (1973) Organic Chemistry. Boston, MA: 
Allyn and Bacon. 

12 Lloyd RV, Fong AJ, Sayre RM. (2001) In Vivo formation of 
Maillard reaction free radicals in mouse skin. J Invest Dermatol 
117, 740-2. 

13 Puccetti G, Tranchant JF, Leblanc RM. (1999) The stability and 
penetration of epidermal applications visualized by photoacous¬ 
tic depth profilometry. Sixth Conference International Society 
of Skin Imaging, Skin Research and Technology, Berlin, 
Germany. 


14 Puccetti G, Leblanc R. (2000) A sunscreen-tanning compromise: 
3D visualization of the actions of titanium dioxide particles and 
dihydroxyacetone on human epiderm. Photochem Photohiol 71, 
426-30. 

15 Shaath N. (2005) Sunscreens Regulation and Commercial Development. 
Boca Raton, FL: Taylor & Francis Group. 

16 Chaudhuri R. Dihydroxyacetone: Chemistry and Applications in 
Self-Tanning Products. White Paper; 7. 

17 Kurz T. (1994) Formulating effective self-tanners with DHA. 
Cosmet Toiletries 109, 55-60. 

18 United States Code of Federal Regulations. 21CFR740.19, 2003. 

19 Minolta. (1993) Precise Color Communication, Color Control 
from Feeling to Instrumentation. Minolta Camera Co. Ltd. 


143 


Chapter 19: Sunscreens 

Dominique Moyal, 1 Angelike Galdi 2 , and Christian Oresajo 2 

^'Oreal Recherche, Asnieres, France 
2 L'Oreal Research, Clark, NJ, USA 


BASIC CONCEPTS 

• Sunscreens provide photoprotection from UV radiation (UVR). 

• Photoprotection is required for both UVB and UVA radiation. 

• Organic and inorganic filters are used in sunscreens. 

• Sunscreen filters must be carefully combined to achieve esthetically pleasing products with photostability and broad spectrum 
photoprotection. 


Introduction 

Human exposure to UVR from sunlight can cause many 
adverse effects. They involve both UVB (290-320nm) and 
UVA (320-400nm). UVB radiation is mainly responsible for 
the most severe damage: acute damage such as sunburn, and 
long-term damage including cancer. It has a direct impact 
on cell DNA and proteins [I]. Unlike UVB, UVA radiation is 
not directly absorbed by biologic targets [2] but can still 
dramatically impair cell and tissue functions: 

• UVA penetrates deeper into the skin than UVB. It particu¬ 
larly affects connective tissue where it produces detrimental 
reactive oxygen species (ROS). ROS cause damage to DNA, 
cells, vessels, and tissues [3-8]. 

• UVA is a potent inducer of immunosuppression [9,10] and 
there is serious concern about its contribution in the devel¬ 
opment of malignant melanoma and squamous tumors 
[ 11 , 12 ]. 

• Photosensitivity reactions and photodermatoses are pri¬ 
marily mediated by UVA [13]. 

As a result, a major concern has been raised that most 
available sunscreen products are incapable of preventing the 
harmful effects of UVA. It is important to note that under 
any meteorologic condition, the UVA irradiance is at least 
17 times higher than the UVB irradiance. 

For all these reasons, it is evident that sunscreens must 
contain both UVA and UVB filters to cover the entire range 
of harmful radiation. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Regulatory status of sunscreens 

With increased knowledge about UV-induced skin damage 
and particularly the effects of UVA, public education pro¬ 
grams have been developed with an emphasis on the proper 
use of sunscreen products. Many new UV filters have been 
made available in the last decade with improved efficacy and 
safety. The availability of new filters has been slow in some 
countries for regulatory reasons. An example is the USA 
where certain UVA and UVB filters, which are marketed 
elsewhere, are not approved for use. The availability of effi¬ 
cient sunscreen products depends not only on the regulatory 
status of the UV filters but also on the ability to inform the 
consumer about product efficacy with appropriate labels 
based on sun protection factor (SPF) and UVA protection 
levels. 

Sunscreen products can be classified in two main catego¬ 
ries according to their purpose: 

1 Primary sunscreens. Products whose main purpose is the 
protection of the skin from the effects of the sun, such as 
beach sunscreens and products used for outdoor activities. 

2 Secondary sunscreens. Products that have a primary use 
other than skin protection, such as daily moisturizing 
creams, antiwrinkle/antiaging creams, and whitening skin 
products. In these products, sun protection is necessary to 
optimize the claimed effect. For this category of products, 
sun protection is an additional claim but not the main 
purpose. 

Sunscreen classification 

Sunscreen products can also be classified in terms of regula¬ 
tory status. Sunscreen products are ordinary cosmetic prod¬ 
ucts in Europe, EU and non-EU countries (e.g. Russia), most 
African and Middle-Eastern countries, India, Latin America, 


144 







19. Sunscreens 


and Japan. They can be classified "special" cosmetic products 
as in China (special cosmetics), Korea and Ethiopia (func¬ 
tional cosmetics), South Africa (under SABS standard), 
Australia (under standards) [14], and Taiwan (medicated 
cosmetics). They are over-the-counter (OTC) drugs in the 
USA [15] (all sunscreens and products with SPF). In Canada, 
they can be either OTC drugs or natural health products 
(NHP), in this case the sunscreen contains only "natural" 
active ingredients: titanium dioxide, zinc oxide. 

Approved UV filters 

In Europe, the UV filters are fisted in Annex VII of the 
Cosmetics Directive. There are 27 UV filters on this list. In 
the USA, there are 16 filters included in the sunscreen 
monograph (Table 19.1). There are two main regulatory 
methods to market OTC products: monograph or a New 
Drug Application (NDA). An NDA is necessary to obtain the 
approval of a formula containing a new UV filter, or a new 
concentration for an approved active, or a new mixture of 
approved actives. 

A Time and Extent Application (TEA) is a new procedure 
for an active ingredient already approved abroad. It allows 
the FDA to accept commercial data obtained on external 
markets in place of use of an authorized drug on the US 
market; however, toxicologic data requirements for a TEA 
are very similar to those for an NDA. 

Seven UV filters are currently eligible for evaluation 
through a TEA procedure (not yet finalized): 


1 Isoamyl p-methoxycinnamate (amiloxate) 10% max. 

2 Methyl benzylidene camphor (enzacamene) 4% max. 

3 Octyl triazone 5% max. 

4 Methylene bis-benzotriazolyl tetramethylbutylphenol 
(Tinosorb® M, Ciba, Basel, Switzerland). 

5 Bis-ethylhexyloxyphenol methoxyphenol triazine 

(Tinosorb® S, Ciba, Basel, Switzerland). 

6 Diethylhexyl butamido triazone 3% max 7 
Terephthalylidene dicamphor sulfonic acid (Ecamsule, 
Mexoryl® SX). 

In Australia, 26 UV filters are accepted by Therapeutic 
Goods Administration (TGA) and in Japan 31 UV filters are 
allowed. 

When comparison is made between the common UV 
filters approved in Europe and USA, only 11 filters are 
common, but p-aminobenzoic acid (PABA) will most likely 
be deleted in Europe and terephtalilydene dicamphor sul¬ 
fonic acid (TDSA) is only available in USA under NDA for 
four formulas. 

Because of the importance of being well protected against 
UVA radiation, there are many new UVA filters or broad 
UVB/UVA filters, which have been developed and author¬ 
ized in Europe, Australia, and Japan. It is obvious that the 
number of these filters is limited in the USA (Table 19.2). In 
addition, there are some limitations in the use of avoben- 
zone in the USA. Combinations with some other UV filters, 
such as titanium dioxide and enzulizole, are not permitted 
and the maximum use level according to the sunscreen 
monograph is limited to 3%. 


Table 19.1 Sunscreen approved in the USA. 

Sunscreen approved in USA 

Maximum concentration (%) 

p-Aminobenzoic acid (PABA) 

15 

Avobenzone 

3 

Cinoxate 

3 

Dioxybenzone 

3 

Ensulizole (phenylbenzimidazole 
sulfonic acid) 

4 

Homosalate 

15 

Meradimate (menthyl anthranilate) 

5 

Octinoxate (octyl 
methoxycinnamate) 

7.5 

Octisalate (octyl salicylate) 

5 

Octocrylene 

10 

Octyl dimethyl PABA 

8 

Oxybenzone 

6 

Salisobenzone 

10 

Titanium dioxide 

25 

Trolamine salicylate 

12 

Zinc oxide 

25 


Development of sunscreens 

A proper sunscreen product must fulfill the following critical 
requirements: 

• Provide efficient protection against UVB and UVA 
radiation; 

• Be stable to heat and to UVR (photostable); 


Table 19.2 Regulatory approval status for the main UVB/UVA and 
UVA filters. 


Benzophenone Oxybenzone 

EU, Japan, Aus, Can, USA 

BMDM (avobenzone) 

EU, Japan, Aus, Can, USA 

TDSA (Mexoryl SX) 

EU, Japan, Aus, Can, USA (NDA) 

DTS (Mexoryl XL) 

EU, Japan, Aus, Can 

DPDT (Neo-Heliopan AP) 

EU, AUS 

DHHB (Uvinul A+) 

EU, Japan 

MBBT (Tinosorb M) 

EU, Japan, Aus 

BEMT (Tinosorb S) 

EU, Japan, Aus 

Titanium dioxide 

EU, Japan, Aus, Can, USA 

Zinc oxide 

Japan, Aus, Can, USA 


145 










HYGIENE PRODUCTS Moisturizers 


• Be user-friendly to encourage frequent application and 
provide reliable protection; and 

• Be cost-effective. 

In order to protect against both UVB and UVA, the sun¬ 
screen product must contain a combination of active ingre¬ 
dients within a complex vehicle matrix. 

Active ingredients can be either organic or inorganic UV 
filters. According to their chemical nature and their physical 
properties, they can act by absorption, reflection, or diffu¬ 
sion of UVR. 

Organic UV filters 

How do organic filters work? 

Organic filters are active ingredients that absorb UVR energy 
to a various extent within a specific range of wavelength 
depending on their chemical structure [16]. The molecular 
structure responsible for absorbing UV energy is called a 
chromophore. The chromophore consists of electrons 
engaged into multiple bond sequences between atoms, gen¬ 
erally conjugated double bonds. An absorbed UV photon 
contains enough energy to cause electron transfer to a 
higher energy orbit in the molecule [16]. The filter that was 
in a low-energy state (ground state) transforms to a higher 
excited energy state. From an excited state, different proc¬ 
esses can occur: 

• The filter molecule can simply deactivate from its excited 
state and resume its ground state while releasing the 
absorbed energy as unnoticeable heat. 

• Structural transformation or degradation may occur and 
the filter losses its absorption capacity. The filter is then said 
to be photo-unstable. 

• The excited molecule can interact with its surroundings, 
other ingredients of the formula, ambient oxygen, and thus 
lead to the production of undesirable reactive species. The 
filter is said to be photoreactive. 

The control of filter behavior under UV exposure is a critical 
point that needs to be investigated when new sunscreen 
products are developed. 

Inorganic UV filters 

Pigment grade powders of metal oxides such as titanium 
dioxide or zinc oxide have been used for many years in 
combination with organic filters to enhance protection level 
in the longer UVA range. Unlike organic filters, they work 
by reflecting and diffusing UVR. However, as a result of the 
large particle sizes, these powders also diffuse light from the 
visible range of the sun spectrum and they tend to leave a 
white appearance on the skin. To overcome this drawback, 
which affects cosmetic acceptance, micronized powders 
of both titanium dioxide and zinc oxide have been made 
available. However, micronization leads to changes in the 
protective properties of titanium dioxide: the smaller parti¬ 
cles shift the protection range from the longer UVA toward 
the UVB. 


Zinc oxide has better absorption in the long UVA than 
titanium dioxide, but it is not very efficient. Because of 
possible photocatalytic activity, inorganic particles are fre¬ 
quently coated with dimethicone or silica for maintenance 
of their efficacy. When nanosized titanium dioxide (<100 nm) 
is combined with organic UV filters, it allows high SPF prod¬ 
ucts to be formulated with a lower dependence on organic 
UV filters. In combination with organic UV filters, nanosized 
titanium dioxide has more a synergistic rather than only an 
additive effect. 

Steps toward more efficient sunscreens 

As far as UVB protection is concerned, a large choice of 
filters has been available for a number of years. They are 
photostable except for the most common, ethylhexyl 
methoxy cinnamate (EHMC). The choice of UVA filters 
depends on the countries and is limited in the USA, as 
already explained. Inorganic pigments offer poor protection 
against UVA when used alone. Benzophenones are photo¬ 
stable but they are primarily UVB filters with some absorp¬ 
tion in the short UVA range (peak at 328nm). 

Butyl methoxy dibenzoyl methane (BMDM or avoben- 
zone) has a high potency in the UVA1 range peaking at 
338nm; however, it undergoes significant degradation 
under UV exposure and this leads to a decrease in its protec¬ 
tive UVA efficacy. Research on the photochemistry of filters 
has led to the identification of some potent photostabilizers 
(e.g. octocrylene) of avobenzone and the development of 
new UVA filters that have a photostable structure. Recently, 
in 2003, diethylamino hydroxybezoyl hexyl benzoate 
(DHHB) was approved in Europe and Japan. This UVA1 filter 
has UV-spectral properties similar to BMDM but DHHB is 
photostable. 

In order to provide full protection in the entire UVA range, 
it is necessary to have efficient absorption in the short UVA 
range. TDSA or Mexoryl SX™ (Chimex, Le Thillay, France), 
with a peak at 345 nm at the boundary between short and 
long UVA wavelengths, was first approved in Europe in 
1993. This was followed by the approval of the broad UVB/ 
UVA filter drometrizole trisiloxane (DTS or Mexoryl XL) 
with two peaks (303 and 344nm) in 1998. Since 2000, other 
short UVA (disodium phenyl dibenzimidazole tetrasulfonate 
[DPDT] or Neo-Heliopan AP®, Symrise, Holzminden, 
Germany, peak at 334nm) and broadband UVB/UVA filters 
(MBBT, Tinosorb M and BEMT, Tinosorb S) have been 
approved in Europe. All these filters are photostable. 

UV filters are either hydrophilic or lipophilic. When com¬ 
bined a synergetic effect can be observed. This property is 
used to obtain higher efficacy against UVB and UVA 
radiation. 

Combinations of highly efficient and photostable filters 
provide an optimally balanced protection against both UVA 
and UVB [17]. Studies [18-20] have shown that the protec¬ 
tion against UV induced skin damage provided by sunscreen 


146 


19. Sunscreens 


products with same SPF but different UVA protection factor 
is markedly different, emphasizing the importance of high 
UVA protection in preventing cell damage. Only well- 
balanced, photostable sunscreens with absorption over the 
entire UV spectrum of sun radiation have been able to 
maintain intact essential biologic functions. 

Formulation types 

Emulsions are the most popular of sunscreen vehicles. They 
offer versatility of texture (cream, lotion, milk) while exhib¬ 
iting good performance. Emulsions can be placed into two 
main categories, oil-in-water (O/W) and water-in-oil (W/O). 
The W/O emulsions are intrinsically very water-resistant 
and will consistently yield higher SPF for the same concen¬ 
tration of sunscreen actives when compared with O/W 
emulsions. However, O/W emulsions are, by far, more 
widely used in sunscreens. This may be explained by the 
lower inherent cost for an O/W vehicle (where water is the 
outer phase) versus a W/O (where oil, a more expensive 
ingredient, is the outer phase). 

Aerosol spray vehicles have grown in popularity over the 
past few years. The multiposition spray nozzles allow for 
quick and easy application. Attention needs to be taken, 
however, that enough product is applied to ensure adequate 
protection. Oil, gel, stick, and mousse vehicles have decreased 
in popularity among formulators and consumers for several 
reasons. They are typically oil or wax-based, which makes 
then rather expensive and less efficacious. Additionally, they 
tend to be oily and greasy which result in lower usage and 
compliance. 


Evaluation of the efficacy of 
sunscreen products 

Evaluation methods must take into account the photo-insta¬ 
bility of products in order to avoid an overestimation of 
protection. In vivo SPF and in vivo UVAPF (Persistent Pigment 
Darkening) test methods take photodegradation into 
account. Appropriate UV doses are used to induce erythema 
on human skin for SPF determination or pigmentation for 
UVAPF determination. 

When in vitro methods are used they should also take into 
account this phenomenon to provide relevant evaluation 
[ 21 ]. 

Evaluation of the sun protection factor 

The international test method for SPF determination was 
first introduced in 2003. This method was published jointly 
by the Japanese Cosmetic Industry Association (JCIA), the 
European Cosmetic Industry Association (Colipa), and the 
Cosmetic Industry Association from South Africa (CTFA SA). 
In 2006, a revised version of this method was published with 
the support of the Cosmetic Toiletries and Fragrance 
Association (CTFA) from the USA [22]. In 1999, the US Food 


and Drug Agency (FDA) published a final monograph [15]. 
FDA received comments and in August 2007 published a 
proposal of amendments [23]. This proposal includes a new 
SPF cap at 50+ and some amendments on technical points 
made in the 1999 monograph on sunscreen products. 

The Australian standards on SPF testing published in 1998 
are similar to the other methods [14]. The International 
Standard Organization (ISO) TC217 WG7 working group is 
currently dealing with the standardization of a SPF method. 
The future ISO standard will be based on the international 
SPF test method including some improvements and it is 
expected to be published at the end of 2009. 

Determination of UVA protection level 

The EU issued a recommendation on September 22, 2006 
[24] to use a persistent pigment darkening (PPD) method 
similar to the JCIA method [25] or any in vitro method able 
to provide equivalent results. In addition, the critical wave¬ 
length [26] must be at least 370nm. The EU Commission 
also recommends that the method used should take into 
account photodegradation. 

The first country that published an official in vivo method 
to assess UVA protection level was Japan. The JCIA adopted 
the PPD method as the official method for assessment of the 
UVA efficacy of sunscreen products in January 1996 [25]. 
Korea and China also adopted this method in 2001 and 
2007, respectively. The PPD method was officially recom¬ 
mended by European Commission in September 2006 [24] 
and was recently proposed by FDA in the 2007 Sunscreen 
Monograph Amendment [23]. The method has been 
described with some minor differences by different countries 
or authorities. Finally, UVA method is currently in progress 
for standardization through the ISO. 

Since the PPD response requires doses greater than 10J/ 
cm -2 (approximately 40 minutes of midday summer sun¬ 
light), the photostability of sunscreens is also challenged 
during the test procedure. To illustrate this point, avoben- 
zone (BMDM, Parsol®1789) was tested [27] at concentra¬ 
tions of 1.0, 3.0, and 5.0% individually and in combination 
with 10% of octocrylene, a UVB filter, known to stabilize 
BMDM. The results of UVA-PF of avobenzone alone ranged 
from 2.2 with 1% BMDM to 4.6 with 5% BMDM. In com¬ 
bination with 10% octocrylene the results ranged from 4.6 
with 1% BMDM to 10.6 with 5% BMDM. It is evident that 
UVA protection efficacy of avobenzone is significantly 
increased when it is combined with octocrylene, compared 
with the same concentration of BMDM alone. This can be 
explained by the fact that the PPD UVA doses affect the 
photostability of BMDM. It has been verified under real sun 
exposure conditions that when a photo-unstable product 
applied at 1 mg/cm 2 is exposed to a UVA dose of about 30 J/ 
cm 2 (about 2.5 hours) there is a dramatic decrease of the 
UVA absorption properties of avobenzone leading to a 
decrease of the UVA protection efficacy [28]. 


147 



HYGIENE PRODUCTS Moisturizers 


Critical wavelength method 

An in vitro approach to measure UVA protection using a thin 
film technique was proposed by Diffey et al. [26]. The UVB 
and UVA absorbance of the product is measured on a film 
of product applied on a substrate which can be quartz or 
polymethyl methacrylate (PMMA). The method yields a 
measure of the "breadth" of UVA protection using a test 
method called "critical wavelength" [26]. In this test pro¬ 
posal, the absorbance of the thin film of the sunscreen is 
summed (starting at 290 nm) sequentially across the UV 
wavelengths until the sum reaches 90% of the total absorb¬ 
ance of the sunscreen in the UV region (290-400nm). The 
wavelength at which the summed absorbance reaches 90% 
of total absorbance is defined as the "critical wavelength" 
and is considered to be a measure of the breadth of sun¬ 
screen protection. 

The critical wavelength A, c is defined according to equation 
(19.1): 

rK f 400 

\g[l/T(k)\dX = 0.9- lg [1 /T(k)]dX (equation 19.1) 

J290 J 290 

Because this is a relative measurement, the "absolute" 
absorbance of the sunscreen is not necessary, eliminating 
the operator dependence of the test method. Critics of the 
methods based on absorbance criteria point to the fact that 
it is not a true measurement of UVA protective potency of 
the test product. The critical wavelength determination (X c ) 
addresses the broadness of the protection rather than the 
specific protection in the UVA. Products with widely differ¬ 
ent in vivo protection indices (i.e. UVAPF PPD) can have 
identical critical wavelengths [29]. Combining both the in 
vivo PPD method for measuring the level of UVA protection 
efficacy and the critical wavelength method to measure the 
broadness of UVA absorbance has been proposed for UVA 
protection assessment of sunscreen products by the European 
Commission [24]. Other studies have shown that the higher 
the UVA protection level as assessed by the PPD method the 
better the protection against damage induced by UVA radia¬ 
tion [18-20]. On the other hand, critical wavelength higher 
than 370 nm is not a sufficient, reliable criterion to ensure 
that a product can provide efficient protection against UVA 
damage. 


Conclusions 

It is important that a minimal proportionality between UVA 
and UVB protection be ensured in order to avoid high UVB 
protection with low UVA protection. A UVAPF: SPF ratio of 
at least one-third as defined by the European Commission 
[24] should be universally adopted for harmonization of 
consumer protection. In order to reach balanced protection, 
combination of UV filters is necessary. The criteria of choice 
are the following: UV filters with different maximum absorb¬ 


ance peaks (UVB, short UVA, and long UVA) to cover the 
entire UV spectrum, appropriate filters in different phases of 
sunscreen emulsion (lipophilic and hydrophilic), and ensur¬ 
ing the photostability of the UV filters. A high level of effi¬ 
cacy and protection against UVB and UVA radiation can be 
achieved by using available new filters. 

References 

1 Urbach F. (2001) The negative effect of solar radiation: a clinical 
overview. In: Giacomoni PU, ed. Sun Protection in Man , ESP 
Comprehensive Series in Photosciences. Vol. 3. Amsterdam: Elsevier 
Sciences, pp. 41-67. 

2 Peak MJ, Peak JG. (1986) Molecular photobiology of UVA. In: 
Urbach F, Gange RW, eds. The Biological Effects of UVA Radiation. 
New York: Praeger Publishers, pp. 42-52. 

3 Lavker RM, Kaidbey K. (1997) The spectral dependence for 
UVA-induced cumulative damage in human Skin. J Invest 
Dermatol 108, 17-21. 

4 Lavker R, Gerberick G, Veres D, Irwin C, Kaidbey K. (1995) 
Cumulative effects from repeated exposures to suberythemal 
doses of UVB and UVA in human skin. J Am Acad Dermatol 32, 
53-62. 

5 Lowe NJ, Meyers DP, Wieder JM, Luftman D, Bourget T, Lehman 
MD, et al. (1995) Low doses of repetitive ultraviolet A induce 
morphologic changes in human skin. J Invest Dermatol 105, 
739-43. 

6 Seite S, Moyal D, Richard S, de Rigal J, Leveque JL, Hourseau 
C, et al. (1997) Effects of repeated suberythemal doses of UVA 
in human skin. Eur J Dermatol 7, 204-9. 

7 Seite S, Moyal D, Richard S, de Rigal J, Leveque JL, Hourseau 
C, et al. (1998) Mexoryl SX: a broadspectrum absorption UVA 
filter protects human skin from the effects of repeated subery¬ 
themal doses of UVA. J Photochem Photobiol B Biol 44, 69-76. 

8 Moyal D, Fourtanier A. (2004) Acute and chronic effects of UV 
on skin. In: Rigel DS, Weiss RA, Lim HW, Dover JS, eds. 
Photoaging. New York: Marcel Deklcer, pp. 15-32. 

9 Moyal D, Fourtanier A. (2002). Effects of UVA radiation on an 
established immune response in humans and sunscreen efficacy. 
Exp Dermatol 11 (Suppl 1), 28-32. 

10 Kuchel J, Barnetson R, Halliday G. (2002) Ultraviolet A aug¬ 
ments solar-simulated ultraviolet radiation-induced local sup¬ 
pression of recall responses in humans. J Invest Dermatol 118, 
1032-7. 

11 Garland CF, Garland FC, Gorham EC. (2003) Epidemiologic 
evidence for different roles of ultraviolet A and B radiation in 
melanoma mortality rates. Ann Epidemiol (AEP) 13395-404. 

12 Agar NS, Halliday GM, Barnetson RS, et al. (2004) The basal 
layer in human squamous tumors harbors more UVA than UVB 
fingerprint mutations: a role for UVA in human skin carcinogen¬ 
esis. Proc Natl Acad Sci USA 101, 4954-9. 

13 Moyal D, Binet O. (1997) Polymorphous light eruption (PLE): 
its reproduction and prevention by sunscreens. In: Lowe NJ, 
Shaat N, Pathak M, eds. Sunscreens: Development and Evaluation 
and Regulatory Aspects , 2nd edn. New York: Marcel Delcker, 
pp. 611-7. 

14 Australian/New Zealand standard AS/NZS 2604 (1998) Sunscreen 
Products: Evaluation and Classification. Standards Australia and 
New Zealand. 


148 



19. Sunscreens 


15 Department of Health and Human Services, Food and Drug 
Administration (USA). (1999) Sunscreen drug products for 
over-the-counter human use. Fed Register 43, 24666-93. 

16 Kimbrough DR. (1997) The photochemistry of sunscreens. 
JChemEd 74, 51-3. 

17 Marrot L, Belaidi J, Lejeune F, Meunier J, Asselineau D, Bernerd 
F. (2004) Photostability of sunscreen products influences the 
efficiency of protection with regard to UV-induced genotoxic or 
photoaging-related endpoints. Br J Dermatol 151, 1234-44. 

18 Fourtanier A, Bernerd F, Bouillon C, Marrot L, Moyal D, Seite 
S. (2006) Protection of skin biological targets by different types 
of sunscreens. Photodermatol Photoimmunol Photomed 22, 22-32. 

19 Moyal D, Fourtanier A. (2001) Broad spectrum sunscreens 
provide better protection from the suppression of the elicitation 
phase of delayed-type hypersensitivity response in humans. 
J Invest Dermatol 117, 1186-92. 

20 Damian DL, Halliday GM, Barnetson RSC. (1997) Broad spec¬ 
trum sunscreens provide greater protection against ultraviolet- 
radiation-induced suppression of contact hypersensitivity to a 
recall antigen in humans. J Invest Dermatol 109, 146-51. 

21 Colipa. (2007) Method for the in vitro determination of UVA 
protection provided by sunscreen products. Guidelines. 

22 Colipa, JCIA, CTFA SA, CTFA. (2006) International Sun 
Protection Factor (SPF) Test Method. 


23 Department of Health and Human Services. Food and Drug 
Administration. (2007) CFR Parts 347 to 352. Sunscreen drug 
products for OTC human use: proposed amendment of final 
monograph; proposed rule. 

24 European Commission Recommendation on the efficacy of 
sunscreen products and the claims made relating thereto. OJL 
265/39, (26.9.2006). 

25 Japan Cosmetic Industry Association (JCIA). (1995) Japan 
Cosmetic Industry Association measurement standard for UVA 
protection efficacy. November 15. 

26 Diffey BL, Tanner PR, Matts PJ, Nash JF. (2000) In vitro assess¬ 
ment of the broadspectrum ultraviolet protection of sunscreen 
products. J Am Acad Dermatol 43, 1024-35. 

27 Moyal D, Chardon A, Kollias N. (2000) UVA protection efficacy 
of sunscreens can be determined by the persistent pigment dark¬ 
ening (PPD) method. Part 2. Photodermatol Photoimmunol Photomed 
16, 250-5. 

28 Moyal D, Refregier JL, Chardon A. (2002) In vivo measurement 
of the photostability of sunscreen products using diffuse reflect¬ 
ance spectroscopy. Photodermatol Photoimmunol Photomed 18, 
14-22. 

29 Forestier S. (1999) Pitfalls in the in vitro determination of critical 
wavelength using absorbance curves. SOFW J 125, 8-9. 


149 


Part 3: Personal Care Products 


Chapter 20: Antiperspirants and deodorants 

Eric S. Abrutyn 

TPC2 Advisors Ltd. Inc. Boquete, Chiriqui, Republic of Panama 


BASIC CONCEPTS 

• Antiperspirants are US Food and Drug Administration (FDA) regulated drugs to be used in the underarm axilla vault only. 

• Antiperspirants are primarily complexes of aluminum (e.g. Aluminum Chlorohydrate) and aluminum zirconium (e.g. Aluminum 
Tetrachlorohydrex-GLY). 

• Deodorants, not to be confused with antiperspirants, are cosmetics and do not typically contain any aluminum-type salt 
complexes. 

• Antiperspirants are associated with few dermatologic issues; slightly irritating under certain conditions, but not scientifically 
associated with breast cancer or Alzheimer disease. 


Introduction 

This chapter deals with the technologies for wetness and 
odor protection of the human axilla, how they are applied, 
and potential adverse effects of use of these products on a 
regular basis. Antiperspirants and deodorants have been 
used for centuries, 1 evolving from simple fragrances that 
masked offensive odors to today's complex ingredients based 
on aluminum and zirconium chemistries that act to slow or 
diminish sweat production. Odors (scents) and sweating 
have a biologic significance. Body scents are primeval and 
most likely evolved genetically to attract the opposite sex. 
Sweating is regulated by the sympathetic nervous system and 
is an important body temperature regulator, especially in 
warm weather climates or during heavy exercise, and func¬ 
tions to remove waste and toxic by-products of the body. The 
axilla area of the body represents a small contribution to 
sweating to control body temperature and removal of bio¬ 
logic by-products, so the controlling of sweat from this area 
has less health risks than other portions of the body. There 
is little scientific evidence that supports the use of antiper- 


^ver 5500 years ago, every major civilization has left a record of its 
efforts to mask body odors. The early Egyptians recommend following 
a scented bath with an underarm application of perfumed oils (special 
citrus and cinnamon preparations). 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


spirants, based on aluminum or aluminum-zirconium 
chemistry causes appreciable lasting adverse effects other 
than possible temporary and reversible irritation. 


Physiology 

Sweat glands and how they work 

Sweat by itself is odorless and only establishes a character¬ 
istic odor when exposed to moisture (humidity) in the pres¬ 
ence of bacterial flora on the skin surface, breaking down 
the sweat's composition and resulting in unpleasant odors. 
The use of antimicrobial agents is a good defense in prevent¬ 
ing odor development from bacteria and yeast present on 
the skin. Another defense is the reduction of excretion from 
the eccrine gland to minimize the appearance of uncomfort¬ 
able or unsightly wetness production. 

According to Gray's Anatomy [1], most people have several 
million sweat glands distributed over their bodies, to include 
the underarm axilla and thus providing plenty of opportu¬ 
nity for underarm odors to develop. Skin has two types of 
sweat glands: eccrine glands and apocrine glands (Figures 
20.1 and 20.2). Eccrine glands open directly on to the surface 
of the skin and exude sweat in the underarm, subsequently 
contributing to odor formation. These glands are located in 
the middle layer of the skin called the dermis, which is also 
made up of nerve endings, hair follicles, and blood vessels. 
Sweat is produced in a long coil embedded within the dermis 
where the long part is a duct that connects the gland to the 
opening (pore) on the skin's surface. When body tempera¬ 
ture rises, the autonomic nervous system stimulates these 


150 










20. Antiperspirants and deodorants 


Figure 20.1 Underarm sweat gland mechanism. 


Eccrine sweat 


H 2 0, Na+ K + f Cl - 
Urea, lactic acid, ammonia 
Traces of amino acids 
and proteins 


^Apocrine^weatJ 

H 2 0 anorganic substances 
S-containing organic substances, lipids 
Steroids, pheromones 



No odor 


4 

Bacterial growth 

I 

Unpleasant odor 


^\ 


Deodorants 


Antiperspirants 

Less odor or not noticed 


Less sweat 


Perfume 

Antibacterials (preservatives) 
Smell 'catchers' 


Aluminium derivatives 
Water-soluble salts 
AIC13 or AI2CI6 first on market 
AI(OH)6CI3 • H 2 0 
AlZr(OH)CI • H 2 0 



Figure 20.2 Cross-section of skin and sweat glands. 


151 




















































HYGIENE PRODUCTS Personal Care Products 


Iso-valeric acid 3-methyl 4-hexanoic Androstenone 



Figure 20.3 Sweat metabolism cycle. 


glands to secrete fluid on to the surface of skin, where it 
then cools the body as it evaporates. The composition of the 
eccrine gland secretion is about 55-60% fluid, mostly water 
with various salts (Primarily: sodium chloride, potassium 
chloride) and various electrolytic components (ammonia, 
calcium, copper, lactic acid, potassium, and phosphorus). 
The warmth and limited air flow is conducive to allowing 
for rapid decomposition of organic matter made up of 
primarily low molecular weight volatile fatty acids (Figure 
20.3). These fatty acids and the steroidal compounds produce 
the recognizable body odors. 

The apocrine glands are triggered by emotions. These 
glands are dormant until puberty, at which time they start 
to secrete. Apocrine glands secrete a fatty substance. When 
under emotional stress, the wall of the tubule glands con¬ 
tract to push the fatty exudates to the surface of skin where 
bacterial flora begin breaking it down. 

In a regulatory monograph [2] the FDA, through the Food 
Drug and Cosmetic Act, defines antiperspirants as an over- 
the-counter (OTC) drug when applied topically to reduce 
production of underarm sweat (perspiration). They are con¬ 
sidered drugs because they can affect the function of the 
body by reducing the amount of sweat that reaches the skin 
surface. In the USA, OTC drugs are subjected to monograph 
rules, which define standards and requirements, premarket 
approval process, acceptable actives, and allowable formula¬ 
tion percentages of actives. Other countries' regulations vary 
in content and scope. Some countries consider antiperspi¬ 
rants as cosmetics and not affecting the biologic physiology 


of the body; as such they are not held to the same strict 
standards as in the USA. As an example, Canada has recently 
(2008) ruled that antiperspirants will longer be considered 
a drug; use of them now only needing to comply with 
cosmetic regulations. 

Wetness and odor control and testing 

The consumer typically confuses what antiperspirants and 
deodorants do, mostly caused by a misunderstanding of 
marketing claims and product positioning. For the most part, 
antiperspirants are based on aluminum-based cationic salt 
chloride complexes (as well as complexes with zirconium 
acid salts) and are referred to as "actives" on back label of 
consumer antiperspirant products. There are numerous 
types of antiperspirant actives listed in the FDA monograph 
as well as in the US Pharmacopia (USP) [3]. Antiperspirant 
actives are responsible for blocking sweat expulsion through 
the formation of temporary plugs within the sweat duct, 
thus stopping or slowing down the flow of sweat to the 
surface of the eccrine gland. 

A theory to wetness control that has been accepted over 
the years is that the hydrated aluminum or aluminum-zir¬ 
conium cationic salt chloride is transported to the eccrine 
gland, interacting with the protein contained within the 
gland. In this basic protein environment, the antiperspirant 
active is reduced, producing a gelatinous proteinaceous plug. 
By plugging the gland, sweat is prohibited from transporting 
to the surface, causing osmotic pressure. Eventually, this 
plug is pushed out of the eccrine gland and the gland is 


152 








20. Antiperspirants and deodorants 


allowed to operate again in a normal fashion. This can take 
14-21 days for all the eccrine gland, to begin firing; known 
as a wash-out period. 

Without going into detail, one can describe how antiper¬ 
spirants are tested for their Wetness Inhibiting Performance 
("WIP"™) 2 effectiveness. The FDA prescribes a methodology 
for testing the effectiveness of an antiperspirant by having 
participants tested in a controlled environment - 30-40% 
relative humidity at approximately 100 °C. Sweat is continu¬ 
ously collected during 20-minute intervals and reported as 
the production or percentage change in production over the 
average of two 20-minute collection periods. To be accepted 
as a participant one must exceed production of 100 mg col¬ 
lected sweat per 20-minute period and should not exceed 
more than 600 mg difference between the highest and 
lowest sweat production within the test population. The 
results of testing need to meet a minimum of 20% sweat 
reduction in 50% of the test population in order to be con¬ 
sidered an antiperspirant. 

Deodorants cover odor through a variety of mechanisms, 
which include the neutralization or counteracting of odor¬ 
iferous axilla odor through the retardation of the odor devel¬ 
opment, or the reduction in perception of odor through 
masking of the odor. Masking is basically accomplished 
via use of fragrances and other volatile components. 
Neutralization is the chemical reaction to modify low molec¬ 
ular weight fatty acids that are excreted from the apocrine 
gland. One type of neutralization agent is antimicrobials that 
disrupt cell barrier viability causing the bacterial microbes to 
perish (triclosan is one popular example). Deodorants are 
designed to minimize underarm axilla odor, not to reduce 
or eliminate perspiration. So, deodorants are best for those 
people who do not have a problem with sweating yet want 
to feel fresh and odor free. It is important to note that 
deodorants have no antiperspirant physiologic activity, but 
antiperspirants can function both as antiperspirants and 
deodorants; thus, consumers needing odor and wetness 
control will require the use of antiperspirants to achieve 
their needs. 


Chemistry and formulation 
of antiperspirants 

It is important to have some understanding of the chemistry 
of antiperspirants to gain a better appreciation of their physi¬ 
ologic action in the axilla mantle. Antiperspirants are divided 
into two categories of functional aluminum-based and 
zirconium-based actives (typically: aluminum chlorohy- 
drate, aluminum zirconium tetrachlorohydrex-GLY, alumi¬ 


2 Trademarked 2008 and property of Eric Abrutyn, TPC2 Advisors Ltd., 
Inc., Republic of Panama Corporation. 


num zirconium trichlorohydrex-GLY, or aluminum chloride) 
plus an inactive formula matrix for consumer acceptable 
aesthetics. 

The basic building block of antiperspirant actives is based 
on aluminum chemistry in which elemental aluminum is 
reduced in an acidic medium to produce what is traditionally 
known as aluminum chlorohydrate (ACH) with an atomic 
ratio of 2:1 aluminum to chloride. These inorganic cationic 
polymer salts are classified as octahedral complexes of a 
basic aluminum hydroxide, stabilized with an anionic chlo¬ 
ride to maintain their water solubility. Within the mono¬ 
graph boundaries [2], the atomic ratio of aluminum to 
chloride can range from 2:1 to 1:1 within three different 
segmentations (aluminum chlorohydrate, aluminum ses- 
quichlorohydrate, and aluminum dichlorohydrate). 

Antiperspirant actives can also be complexed with 
hydrated acidic zirconium cationic salts of chloride to make 
what is traditionally known as aluminum zirconium chloro¬ 
hydrate (ZAG or AZG). Like ACHs, AZGs can have various 
ratios of atomic aluminum to zirconium of 2:1 to 10:1 and 
atomic total metals to chloride of 0.9:1 to 2.0:1. These AZG 
complexes can be buffered with glycine (an amino acid) to 
stabilize the complex and mitigate the acidic harshness 
which could result when applied to underarm axilla. 

There is a growing interest in aluminum-free odor and 
wetness controlling products. One product that has emerged 
is based on a natural stone "crystal." "Crystal" products are 
made from a mineral known as potassium alum, also known 
as potassium aluminum sulfate and contain aluminum. 
Unlike aluminum salts used in antiperspirants, alum does 
not prohibit sweating; it only helps control the growth of 
bacteria that can cause an underarm odor. 


Delivery systems 

The formulation matrix delivery system is the key to effec¬ 
tiveness of antiperspirant active performance and acceptable 
consumer application. The most common delivery systems 
are roll-ons (either aqueous or cyclosiloxane suspensions), 
aerosol (hydrocarbon propellant suspensions), extrudable 
clear gels (water-in-cyclosiloxane emulsions), extrudable 
opaque soft solids (anhydrous cyclosiloxane suspension 
pastes), or sticks (anhydrous cyclomethicone suspension 
solids) (Figure 20.4). Within each form there are typical 
inactive ingredients that support a stable formula with con¬ 
sumer-acceptable esthetics so as not to interfere with the 
WIP™ delivery of the antiperspirant active. 

Although this chapter does not focus on details of formu¬ 
lation development, this subject can be researched in more 
detail in the literature [4,5]. In general, aqueous-based 
hydrous formulas (mostly based on roll-on and clear gel 
delivery systems) will have some type of emulsifier or sta¬ 
bilizing agent. In the case of aqueous roll-ons, they tend to 


153 





HYGIENE PRODUCTS Personal Care Products 



Gel 


16% Cyclics 

1% Dimethicone 
copolyol 

50% AP salts in 
water 

15% Propylene 
glycol 

17% Water 


□ 

Stick 

40-50% Cyclics 

20-25% AP salts 
(no water) 

15-25% Waxes 

0-10% Others 



25% AP salts 

11% Organic 
emulsifier 

4% Organic 
thickener 



45-75% Cyclics 
20-25% AP salts 
2-4% Bentone 
0-10% Other 


Aerosol 

8-15% Silicones 
8-15% AP salts 
2% Bentone 
75-85% Propellant 


Figure 20.4 Antiperspirant formula matrix delivery systems. 


be Polyethylene Glycol (PEG) or Polypropylene Glycol (PPG) 
ethoxylated alcohols (INCI e.g.: PEG-2, PEG-20) and for 
clear gel emulsions they are based on PEG and PPG alkoxy- 
lated functional siloxanes (INCI e.g.: PEG/PPG-18/18 
Dimethicone Copolymer). Anhydrous-based formulas (typi¬ 
cally: solid sticks, some types of roll-ons, extrudable creams) 
include cyclosiloxane (preferably Cyclopentasiloxane) for 
transient solvent delivery of the active and its eventual evap¬ 
oration to leave no residue on the skin, solidification agent 
(INCI e.g.: Stearyl Alcohol, Hydrogenated Castor Oil, and 
miscellaneous fatty acid ester wax), and dispersing agent 
(INCI e.g.: PPG-14 Butyl Ether). Most antiperspirant formu¬ 
las include other ingredients for cosmetic purposes, such as 
fragrance, antioxidants (BHT - Butylated Hydroxytoluene), 
chelating agents (Disodium EDTA - Disodium Edetate), soft 
feel powders (Talc, Corn Starch, and Corn Starch Modified), 
and emollients and/or moisturizers (petrolatum, mineral oil, 
fatty acid esters, non-volatile hydrocarbons). These ingredi¬ 
ents have been used in the industry for well over 25 years 
with accepted safety profiles; reviewed by Cosmetic 
Ingredient Review (http://www.cir-safety.org/) and other 
governmental or medical agencies. 


Dermatologic concerns 

Each manufacturer of antiperspirants keeps a thorough 
record of adverse affects as reported by the consumer. For 
the most part, there is a low incident of adverse affects when 
the product is use as prescribed. Issues tend to revolve 
around skin irritation and sensitization. These adverse affects 
are reversible with cessation of use. Irritation can be brought 


about for a number of reasons, but most often by application 
on broken skin (e.g. from shaving) or sensitivity to the fra¬ 
grance or one of the metallic components of the antiperspi¬ 
rant active. Switching brands or fragrances types is one 
remedy to alleviate adverse affects. In some cases a person 
is so sensitive to an antiperspirant active that he or she can 
no longer use a product containing an aluminum-based 
antiperspirant. 

Health concerns regarding antiperspirants have been dis¬ 
cussed in the literature over the last 40-50 years and mostly 
relate to breast cancer or Alzheimer disease. According to 
the Alzheimer's Association (http://www.alz.org/index.asp), 
the linkage of aluminum and Alzheimer disease is most 
likely linked to a single study in the 1960s where an abnor¬ 
mally high concentration of aluminum was observed in the 
brains of some Alzheimer patients. However, "After several 
decades of research," reports the Alzheimer's Association, 
"scientists have been unable to replicate the original 1960s 
study." In fact, there is still no scientific correlation on the 
cause and effect relationship for contracting Alzheimer 
disease. The research community is generally convinced that 
aluminum is not a key risk factor in developing Alzheimer 
disease. Public health bodies sharing this conviction include 
the World Health Organization, the US National Institutes 
of Health, the US Environmental Protection Agency, and 
Health Canada. 

According to the National Cancer Institute (NCI) and the 
American Cancer Society, rumors connecting antiperspirant 
use and breast cancer are largely unsubstantiated by scien¬ 
tific research. The rumors suggest that antiperspirants 
prevent a person from sweating out toxins and that this 
helps the spread of cancer-causing toxins via the lymph 


154 









































20. Antiperspirants and deodorants 


nodes. The NCI discusses two studies that address the breast 
cancer rumor. A 2002 study of over 800 patients at the Fred 
Hutchinson Cancer Research Institute found no link between 
breast cancer and the use of antiperspirant and/or deodorant 
[6]; and a study of 437 cancer patients, published in 2003 
in the European Journal of Cancer Prevention, found no correla¬ 
tion between earlier diagnosis of breast cancer and antiper¬ 
spirant and/or deodorant use [7]. The NCI's analysis of the 
second study was that it "Does not demonstrate a conclusive 
link between these underarm hygiene habits and breast 
cancer. Additional research is needed to investigate this rela¬ 
tionship and other factors that may be involved." 

Through the evaluation of these and other independent 
studies, it can be concluded that there is no existing scientific 
or medical evidence linking the use of underarm products 
to the development of breast cancer. The FDA (Food & Drug 
Administration), the Mayo Clinic, the American Cancer 
Society, and the Personal Care Products Council (formerly 
Cosmetic, Toiletry, and Fragrance Association) have come 
to a similar conclusion. 

Sweating is necessary to control body temperature, espe¬ 
cially during times of exercise and warm or hot surround¬ 
ings. In a small portion of the population the sympathetic 
nervous system can go awry, affecting the complex biologic 
mechanism of perspiration, resulting in either excessive per¬ 
spiration (hyperhidrosis) or little or no perspiration (anhid¬ 
rosis). Currently, there are no known cures for hyperhidrosis 
but there are a number of treatment options: injectable 
treatment such as botulinum toxin type A (Botox), topical 
agents such as prescribed antiperspirants, oral medications, 
and surgery. 

Based on information from the International Hyperhidrosis 
Society, over 87% of people with hyperhidrosis say that OTC 
antiperspirants do not provide sufficient relief. Thus, it is 
important for the medical community to understand the 
other options available to treat excessive sweating. Botox, a 
drug that has been approved for use as an injectable treat¬ 
ment in the axilla area, works to interrupt the chemical 
messages (anticholinergic) released by nerve endings to 
signal the start of sweat production. It is important to under¬ 
stand how to administer Botox in a manner that will not 
cause medical issues, thus only a trained practitioner should 
administer treatment. Unfortunately, Botox is not a perma¬ 
nent solution, and patients require repeat injections every 
6-8 months to maintain benefits. 

There are other options for treating excessive sweating, 
but none have been demonstrated to be either safe or effec¬ 
tive for use by consumers. Most systemic medications, in 
particular anticholinergics, reduce sweating but the dose 
required to control sweating can cause significant adverse 
effects (e.g. dizziness), thus limiting the medications' effec¬ 
tiveness. Iontophoresis is a simple and well-tolerated method 
for the treatment of hyperhidrosis without long-term adverse 
effects; however, long-term maintenance treatment is 


required to keep patient's symptom free. Psychotherapy has 
been beneficial in a small number of cases. 


Strengths and weakness of antiperspirants 

Based on all the information known about antiperspirants 
one would surmise there are few weaknesses regarding the 
use of them. Basically, they serve the purpose of reducing 
the discomfort and potential observation of underarm 
wetness, and can lead to reduced underarm offensive odors. 
Except in the case of hyperhidrosis, antiperspirants serve to 
provide cosmetic esthetics and social acceptance. It is impor¬ 
tant to note that, even if used twice a day, antiperspirants 
do not completely stop axilla sweating, but provide a signifi¬ 
cant reduction in the amount of sweating produced in the 
axilla. With almost 70 years of use for antiperspirant actives, 
there is almost no association with adverse affects when 
properly used in the underarm area. So, the risk-benefit is 
minimal and is balanced by the ability to maintain a more 
comfortable and socially appealing state. 


Conclusions 

Because they are regulated in the USA and other countries 
as drugs, it is foreseen that introduction of new antiperspi¬ 
rant actives will be restricted. To introduce new antiperspi¬ 
rant actives, one would have to go through an extensive 
New Drug Application process, requiring costly studies on 
safety and effectiveness. Aside from the introduction of new 
antiperspirant drugs, dermatologists need to continue moni¬ 
toring the introduction of unregulated new ingredients that 
would be included in existing or new formula matrices. 

References 

1 Gray's Anatomy: The Anatomical Basis of Clinical Practice , 39th edn. 
(2004) CV Mosby. 

2 USA Department of Health and Human Services: Food and 
Drug Administration. (2003) Antiperspirant Drug Products for 
Over-the-Counter Human Use, Final Rule. 68 CFR, Part 110. 
http://www.fda.gov/cder/otcmonographs/Antiperspirant/ 
antiperspirant_FR_20030609.pdf 

3 USP 27/NF 22 (2004) United States Pharmacopeial Convention, 
Rockville, MD, pp. 83-91; 93-106. 

4 Abrutyn E. (1998) Antiperspirant and Deodorants: Fundamental 
Understanding. IFSCC Monograph Series No. 6. Weymouth, 
Dorset, UK: Micelle Press. 

5 Abrutyn E. (2000) Antiperspirant and deodorants. In: Reiger 
MM, ed. Harry's Cosmetology , 8th edn. New York: Chemical 
Publishing Company, Inc., 

6 http://jncicancerspectrum.oxfordjournals.org/cgi/reprint/jnci; 
94/20/1578.pdf (Vol. 94, No. 20, Pg 1578, October 16, 2002). 

7 McGrath KG. (2003) An earlier age of breast cancer diagnosis 
related to more frequent use of antiperspirants/deodorants and 
underarm shaving. Eur J Cancer Prev 12, 479-85. 


155 




Chapter 21: Blade shaving 

Keith Ertel 1 and Gillian McFeat 2 

1 Procter & Gamble Co, Cincinnati, OH, USA 

2 Gillette, Reading Innovation Centre, Reading, UK 


BASIC CONCEPTS 

• Hair removal practices have their roots in antiquity. While modern global attitudes towards hair removal vary, consumers around 
the world use blade shaving as a method to effect hair removal. 

• Modern blades and razors are the product of extensive research and technologically advanced manufacturing procedures; these 
combine to provide the user with an optimum shaving experience. 

• Effective shaving involves three steps: preparation, including skin cleansing and hair hydrating; hair removal, including the use 
of an appropriate shaving preparation; and post-shave skin care, including moisturizer application. 


Introduction 

Like many personal care practices, the roots of shaving lie 
in the prehistoric past. Hair removal for our cave dwelling 
ancestors was probably more about function than esthetics; 
hair could provide an additional handle for an adversary to 
grab during battle, it collected dirt and food, and provided a 
home to insects and parasites. Flint blades possibly dating as 
far back as 30 000 bc are some of the earliest examples of 
shaving implements. Archaeologic evidence shows that 
materials such as horn, clamshell, or shark teeth were used 
to remove hair by scraping. Pulling or singeing the hair, 
while somewhat more painful, were also methods used to 
effect hair removal. 

Attitudes towards hair became more varied in ancient 
times. The Egyptian aristocracy shaved not only their faces, 
but also their bodies. The Ancient Greeks viewed a beard as 
a sign of virility but Alexander the Great, who is said to have 
been obsessed with shaving, popularized the practice among 
Greek males. Greek women also shaved; a body free from 
hair was viewed as the ideal of beauty in Greek society. 
Shaving was viewed as a sign of degeneracy in early Roman 
society, but an influx of clean-shaven foreigners gradually 
changed this attitude. For affluent Romans shaving was 
performed by a skilled servant or at a barbershop, which was 
popularized in Ancient Rome as a place of grooming and 
socializing. Shaving implements at this time were generally 
made from metals such as copper, gold, or iron. 

The barbershop took on an expanded role in the Middle 
Ages. In these shops barbers provided grooming services and 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


routinely performed other duties such as bloodletting and 
minor surgical and dental procedures. Shaving injuries were 
common and the striped pole that is today associated with 
barbershops has its origin in these times, its red and white 
stripes symbolizing blood and the bandages that were used 
to cover the wound, respectively. 

The Industrial Revolution heralded a number of advance¬ 
ments in shaving technology. The straight razor was first 
introduced in Sheffield, England and became popular world¬ 
wide as a tool for facial shaving. While an improvement over 
earlier shaving implements, the straight razor dulled easily, 
required regular sharpening or stropping, and a high skill 
level, and shaving injuries were still a problem, which 
earned it the nickname of "cutthroat razor." Many credit 
Jean Jacques Perret with inventing the safety razor in 1762. 
His device, which he apparently did not patent, consisted of 
a guard that enclosed all but a small portion of the blade. 
Variations on the design followed from other inventors, 
many using comb-like structures to limit blade contact with 
the skin. The Kampfe brothers filed a patent in 1880 for a 
razor, marketed as the Star Safety Razor that used a "hoe" 
design in which the handle was mounted perpendicular to 
the blade housing. The blade, essentially a shortened straight 
razor, was held in place by metal clips. While generally suc¬ 
cessful, the blade in the Star Safety Razor still required 
stropping before each use. 

In 1904, King C. Gillette introduced the real breakthrough 
that brought shaving to the masses. Unlike its predecessors, 
the Gillette Safety Razor used an inexpensive, disposable 
blade that was replaced by the user when it became dull. 
The new razor quickly gained popularity because of a variety 
of promotional efforts, including a "loss leader" marketing 
model pioneered by Gillette. 

Shaving was not only promoted to males. The practice of 
shaving among females was prompted by the May 1915 


156 






21. Blade shaving 


issue of Harper's Bazaar magazine that featured a picture of 
a female model wearing a sleeveless evening gown and 
sporting hairless axillae. The Wilkinson Sword Company 
built on the idea by running a series of advertisements tar¬ 
geting women in the 1920s to promote the idea that under¬ 
arm hair was not only unhygienic, but was also unfeminine. 
Sales of razor blades doubled over the next few years. 

Razor developments during the next several decades were 
primarily limited to improvements in single blade technol¬ 
ogy, including the switch from carbon steel to stainless steel 
blade material in the 1960s pioneered by Wilkinson Sword. 
This prevented corrosion, thus increasing blade life. The 
next major change occurred in the 1971 with the introduc¬ 
tion of the Trac II, the first multiblade razor. Innovation has 
continued along this track and today consumers can choose 
from a variety of razor models having multiple blades con¬ 
tained in a disposable cartridge, with specialized designs 
available to meet the shaving needs of both sexes. The rela¬ 
tively simple appearance of these devices belies their sophis¬ 
tication; they are the product of years of development and 
technically advanced manufacturing processes. 

Of course, not all shaving is done with a blade. Electric 
razors remove hair without drawing a blade across the skin. 
There are two basic types of electric razors, both relying on 
a scissor action to cut hairs using either an oscillatory or 
circular motion. When the razor is pressed against skin the 
hairs are forced up into holes in the foil and held in place 
while the blade moves against the foil to cut the trapped 
hairs. Colonel Jacob Schick patented the first electric razor 
in 1928. Electric razors were for many decades confined to 
use on dry skin, but some modern battery-powered razors 
are designed for use in wet environments, including the 
shower. 


Hair biology basics 

Much of the hair targeted for removal by shaving or other 
means is terminal hair (i.e. hair that is generally longer, 
thicker, and more darkly pigmented than vellus hair). In 
prepubescent males and females this hair is found primarily 
on the head and eyebrow regions, but with the onset of 
puberty terminal hair begins to appear on areas of the body 
with androgen-sensitive skin, including the face, axillae, and 
pubic region. Further, vellus hairs on some parts of the body, 
such as the beard area, may convert to terminal hairs under 
hormonal influence. 

The pilosebaceous unit 

A pilosebaceous unit comprises the hair follicle, the hair 
shaft, the sebaceous gland, and the arrector pili muscle. The 
hair follicle is the unit responsible for hair production. Hair 
growth is cyclical, and depending on the stage of hair growth, 
the follicle extends to a depth as shallow as the upper dermis 


to as deep as the subcutaneous tissue during the active 
growth phase. 

The hair shaft is the product of matrix cells in the hair 
bulb, a structure located at the base of the follicle. The hair 
shaft is made up primarily of keratins and binding material 
with a small amount of water. A terminal hair shaft com¬ 
prises three concentric layers. Outermost is the cuticle, a 
layer of cells that on the external hair are flattened and 
overlapping. The cuticle serves a protective function for 
external hair, regulates the water content of the hair fiber, 
and is responsible for much of the shine that is associated 
with healthy hair. The cortex lies inside the cuticle and is 
composed of longitudinal keratin strands and melanin. This 
layer represents the majority of the hair shaft and is respon¬ 
sible for many of its structural qualities (e.g. elasticity and 
curl). The medulla is the inner most layer found in some 
terminal hair-shafts, made up of large loosely connected 
cells which contain keratin. Large intracellular and intercel¬ 
lular air spaces in the medulla to some extent determine the 
sheen and colour tones of the hair. 

Each hair follicle is associated with a sebaceous gland. This 
gland lies in the dermis and produces sebum, a lipophilic 
material composed of wax monoesters, triglycerides, free 
fatty acids, and squalene. Sebum empties into the follicle 
lumen and provides a natural conditioner for the forming 
and already extruded hair. The arrector pili is a microscopic 
band of smooth muscle tissue that connects the follicle to 
the dermis. In certain body sites, when stimulated the arrec¬ 
tor pili contracts and causes the external hair to stand more 
erect, resulting in the appearance of goose bumps. 

Hair growth cycle 

Hair growth is not a continuous process but occurs over a 
cycle that is conveniently divided into three stages; at any 
given time hairs on a given body site are at various points 
in this cycle. The dermal papilla orchestrates the hair growth 
cycle. Anagen is the phase of hair follicle regrowth and hair 
generation. During this stage the hair follicle grows down¬ 
ward into the dermis and epidermal cells that surround the 
dermal papilla undergo rapid division. As new cells form 
they push the older cells upward. The number of hairs in 
anagen varies according to body site. At any given time 
approximately 80% of scalp hairs are in anagen. This is 
lower for beard and moustache hairs (around 70%) and 
only 20-30% for the legs and axillae. The length of the 
anagen phase also varies; on the scalp anagen typically lasts 
from 3 to 6 years, in the beard area this is closer to 1 year 
and in the moustache area anagen lasts from 4 to 14 weeks. 
Anagen is typically 16 weeks for the legs and axillae. The 
time in anagen determines the length of the hair produced 
[!]• 

Anagen is followed by catagen, a transitional phase in the 
hair growth cycle that sets the stage for production of a 
new follicle. In catagen the existing follicle goes through 


157 



HYGIENE PRODUCTS Personal Care Products 


controlled involution, with apoptosis of the majority of fol¬ 
licular keratinocytes and some follicular melanocytes. The 
bulb and suprabulbar regions are lost and the follicle moves 
upward, being no deeper than the upper dermis at phase 
end. The dermal papilla becomes more compact and moves 
upward to rest beneath the hair follicle bulge. On the scalp 
catagen lasts 14-2i days. 

Telogen is a phase of follicular quiescence that follows 
catagen. The final cells synthesized during the previous cycle 
are dumped at the end of the hair shaft to form a "club" that 
holds the now non-living hair in place. These hairs are lost 
by physical action (e.g. combing) or are pushed out by the 
new hair that grows during the next anagen phase. The 
percentage of follicles in telogen also varies by body site (e.g. 
5-15% of scalp follicles are normally in telogen whereas 
30% of follicles on the beard area are normally in telogen 
and 70-80% of leg and axillae hairs). Telogen typically lasts 
for 2-3 months, although this is slightly longer for leg hairs 

[il- 

Properties of hair - impact on shaving 

The beard area of an adult male contains between 6000 and 
25 000 hair fibers and beard growth rate has been reported 
in the literature to be 0.27mm per 24 hours, although this 
can vary between individuals [2]. There are two types of 
hair fibers found in the beard area. Fine, non-pigmented 
vellus hairs are distributed amongst the coarser terminal 
hairs. While the literature abounds in publications on the 
properties of scalp hair, studies of beard hair are relatively 
scarce. 

Tolgyesi et al. [3] published the findings of a comparative 
study of beard and scalp terminal hair with respect to mor¬ 
phologic, physical, and chemical characteristics. Scalp fibers 
were reported to have half the number of cuticle layers 
compared to beard hairs from the same subject (10-i3 in 
facial hair, 5-7 in scalp hair). Scalp fibers also had smaller 
cross-sectional areas (approximately half the area) and were 
less variable in shape than beard hairs, which exhibited 
asymmetrical, oblong, and trilobal shapes. These differences 
can be seen in Figure 21.1. Thozur et al. [4] further showed 
considerable variations in beard hair follicle shape and diam¬ 
eter within and between individuals. A number of factors 
contribute to this variation including anatomical location, 
ethnicity, age, and environmental factors. 

The structural properties of the hair impact shaving. The 
force required to cut a hair increases with increasing fiber 
cross-sectional area [5]. Thus, it requires more force to cut 
a larger fiber. Indeed, it requires almost three times the force 
to cut a beard hair than a scalp or leg hair. One important 
property of hair is that the force required to cut it can be 
greatly reduced by hydrating the hair. Hydration causes the 
hair to become significantly softer and much easier to cut so 
that it offers less resistance to the blade and minimizes any 
discomfort. 



Figure 21.1 Optical micrographs of hair cross-sections taken from the 
beard (a) and scalp (b) area of the same subject. Beard fibers have a 
greater cross sectional area and more cuticle layers. 


The human hair follicle and the surrounding skin are 
richly innervated. In particular, the terminal hairs of the 
human skin are supplied with several types of nerve endings 
most of which are sensory in nature. It is hypothesized that 
discomfort associated with shaving (during shaving or post¬ 
shave) is a result of localized skin displacement and/or the 
rotation and extension of the beard fiber in its follicle. The 
current neurologic literature clearly demonstrates that such 
local cutaneous distortions bring about the release of various 
chemical communicators (e.g. histamine, prostaglandins, 
bradykinins) that heighten the sensitivity of the response of 
pain-mediating nerve endings for a period of time [6]. The 
contribution to shaving comfort and irritation remains to be 
elucidated. 

Shaving can also cause irritation by physical damage. 
There is evidence to suggest that shaving irritation involves 
the removal of irregular elevations of the skin by the razor 
blade, particularly around follicular openings [7,8]. 

The topography of the skin is highly variable and com¬ 
bined with the presence of hairs this creates a very irregular 
terrain over which an incredibly sharp blade traverses 
(Figure 21.2). This can result in irritation, generally charac¬ 
terized in this context by the presence of attributes such as 
nicks or cuts, redness, razor burn, sting, or dryness. In order 
to achieve a close and comfortable shave with minimal irri¬ 
tation it is essential to use a good quality, sharp blade and 


158 



21. Blade shaving 



Figure 21.2 A scanning electron micrograph of a replica of an area of 
cheek on a male face. The topography of the skin is highly variable and 
combined with the presence of hairs this creates a very irregular terrain 
over which an incredibly sharp blade traverses. 


adopt a shave care regimen designed to remove as much 
hair as possible while inflicting minimal damage to the 
underlying skin. 


Shaving and the razor explored 

Since the invention of the safety razor, consumer product 
industries have invested a considerable amount of time, 
money, and expertise in improving the design of the razor 
and blade in order to provide a closer, more comfortable, 
and safer shave. 

To date, few reports have been available in the literature 
detailing the shaving process and the mechanisms involved. 
The following section aims to provide an overview of the 
razor and the complex mechanisms by which the blade cuts 
the beard hair and interacts with the underlying skin. 

Evolution of the system razor 

With a system razor, only the cartridge containing the blades 
is replaced, unlike a disposable razor which is thrown away 
in its entirety when blunt. 

In the first double edge razor systems, the consumer had 
to position and tension a single blade within the handle. As 
a result, there was variability and inconsistency in how the 
blade interacted with the skin. In contrast, the advanced 
shaving systems of today are precisely assembled during 
manufacture. 

Figure 21.3 shows a cross-section of a double edge razor 
with the key parameters of the cartridge geometry indicated. 
The shaving angle is the angle between the center plane of 
the blade and a plane tangent to the guard. The blade expo¬ 
sure is the amount by which the tip of the blade projects 
beyond the plane tangent to the cap and guard. Altering any 



Figure 21.3 Cross-section of a double-edge razor showing exposure 
geometry. 

of these parameters has both good and bad effects. For 
example, an increase in blade exposure brings the blades 
into closer contact with the underlying skin and hair, 
increasing the closeness of a shave at the expense of more 
nicks and cuts and discomfort. A reduction in the shaving 
angle improves comfort but reduces cutting efficiency. 
Consequently, all aspects of the double edge blade system 
were compromises and the user was able to adjust the razor 
to suit their individual preferences [9]. 

Modern systems have reduced the need to compromise 
and achieved the previously unattainable: improving close¬ 
ness, safety, and comfort simultaneously. The improvement 
in closeness is attributed to, and exploits the mobility of the 
hairs within the follicle. Observation of the movement of 
hairs during shaving has shown that they are not cut through 
immediately upon contact with the blade; rather, they are 
carried along by the embedded blade tip, and effectively 
extended out of the follicle. This extension is primarily 
brought about by the distortion of the soft tissue between 
the hair root and the skin surface layers. Because of the 
viscoelastic nature of the tissue, once severed the hair rapidly 
retracts back into the follicle. If a second blade follows 
closely behind the first, it can engage the hair in the elevated 
state, cutting it further down the hair shaft, before it has 
time to fully withdraw into the follicle [9]. By having mul¬ 
tiple blades, this process can be exploited to give a measur¬ 
able improvement in closeness. It is therefore possible to use 
a lower blade exposure to achieve closeness while minimiz¬ 
ing skin contact and thus the potential for nicks, cuts, and 
discomfort. 

Simply adding more blades to razors is not a new idea (the 
first US patent for a 5-blade razor was filed in 1929, 
US1920711) and from the above it is clear that on its own 
this will not deliver a great shave. In addition to precisely 
controlling the razor geometry, it is essential that the under¬ 
lying skin is carefully managed to ensure a safe and comfort¬ 
able shave. Adding more blades improves closeness by virtue 
of hair extension and probability of cutting, but can also 
create drag and discomfort. The pressure exerted on the skin 
by the additional blades can cause the skin to bulge between 


159 





HYGIENE PRODUCTS Personal Care Products 


(a) 


the inter blade span. By spacing the blades closer together, 
both the drag and skin bulge are reduced and a more uniform 
stress is placed on the skin leading to a safer, more comfort¬ 
able shave (Figure 21.4). 

Manipulating these parameters can greatly alter the 
characteristics of a shave; consequently cartridge geometry 
and blade spacing are carefully controlled and set during 
manufacturing using specifications determined through 
extensive research. This ensures that the consumer receives 
a targeted and consistent shave with the optimum blade- 
skin contact. 

Cutting edge technology 

A further critical component of the shaving process, and 
central to a great shave, is the razor blade edge. The nar¬ 
rower the blade edge the more easily it can cut through a 
hair, leading to a closer and more comfortable shave. 
However, if the blade is too narrow it can collapse under the 



Figure 21.4 Multiple blade razors and skin management. Spacing 5 blades 
force for a safer, more comfortable shave. 


cutting force. Thus, the industry strives to produce the thin¬ 
nest blade edge possible while retaining blade edge strength. 
This is typically achieved by treating a stainless steel sub¬ 
strate with thin film coatings such as diamond-like carbon 
to enhance edge strength or platinum-chromium to enhance 
corrosion resistance. The blades are further coated in a 
telomer like material to create a low friction cutting surface. 
This greatly reduces the force required to cut hair, minimiz¬ 
ing hair "pulling," providing additional comfort. 

Additional key components of a modern razor are shown 
in Figure 2L5. First introduced in i985, lubricating strips 
are now found on most disposable and permanent system 
cartridges. The strips distribute water-soluble lubricant fol¬ 
lowing each shaving stroke, resulting in a significant reduc¬ 
tion in drag of the cartridge over the skin and allowing 
additional strokes to be taken comfortably even after most 
of the shaving preparation has been shaved off. The strips 
also allow the skin to release freely from the tension created 



closer together (b), creates a shaving surface that helps spread shaving 



Lubricating strip: 

Low friction, releases 
skin tension, lubricates 
for next stroke 


Fin guard: 

Tensions skin ahead 
of blades 


Pivot: 

Rotation point of cartridge, 
ensure cartridge follows 
contours 


Trimmer blade: 
Precision trimming 


Blade springs: 
Allows blades to 
react to load 


Blades: 

Extend and cut hair 
Interact with skin 


Figure 21.5 The key components of a razor 
and their functions. 


(b) 


160 







21. Blade shaving 


Figure 21.6 Effect of hydration time on force required to cut (beard) 
hair. The most significant reduction occurs over the first 2 minutes. 



by the skin guard. The guard is typically comprised of soft, 
flexible microfins or rigid plastic which precede the blades. 
These microfins gently stretch the skin, causing beard hairs 
to spring upward so they can be cut more efficiently. 
Additional features include pivoting heads that allow the 
cartridge to follow the contours of the face and trimmer 
blades allow the shaver to get exact positioning of the blade 
for a closer, more precise shave. The recent introduction of 
oscillating wet shaving systems increases razor glide for 
improved comfort. 

Such advances in blade edge and razor technology, coupled 
with an understanding of the needs of the consumer, have 
significantly enhanced the quality, closeness, safety, and 
comfort of the shave. This is most evident when combined 
with a shave care regimen designed to maximize hair 
removal and minimize skin damage. 


The shaving process 

Drawing a sharpened implement across the skin's surface 
has the potential to cause damage and dry shaving can result 
in the immediate appearance of uplifting skin cells and per¬ 
turbation of stratum corneum barrier function, with an 
increase in dryness observed several days subsequent to the 
initial damage [10]. Body site will likely influence the 
response to this insult because the number of stratum 
corneum cell layers varies over the body surface, averaging 
10 layers on the cheek or neck and 18 layers on the leg [11]. 
The potential for damage is compounded by non-uniform 
skin surface topography and the presence of hair (Figure 
21.2), which when dry is relatively tough. A dry hair has 
about the same tensile strength as a copper wire of equiva¬ 
lent diameter. 

A few simple steps can help prepare the skin and hair for 
an optimum shaving experience. First, the skin should be 
thoroughly cleansed. Cleansing removes surface soils that 


can interfere with the shaving process and also helps hydrate 
the hair. The latter is especially important and shaving 
during or after showering or bathing is ideal but short of 
this, the area to be shaved should be washed with a cleanser 
and warm water. In some situations applying a warm, wet 
towel or cloth to the skin for a few minutes before shaving 
may also help. Hair is mostly keratin, and keratin has a high 
affinity for water. Hydrating softens the hair to make it more 
pliable and easier to cut; the force required to cut a hair 
decreases dramatically as hydration increases (Figure 21.6). 
Short-term hydration will also improve the skin's elasticity 
[12], making it better able to deform and recover as the 
blade is drawn over its surface. However, more is not neces¬ 
sarily better; prolonged soaking can macerate skin and cause 
the surface to become uneven, making effective hair removal 
more difficult and increasing the risk of damaging the skin. 
Excessive soaking can also deplete the stratum corneum of 
substances such as natural moisturizing factor (NMF) that 
help it hold on to water [13], which can exacerbate any 
dryness induced by the shaving process. 

A preparation such as a shaving gel or cream can also 
improve the shaving experience. A preparation serves 
several functions. The physical act of applying preparation 
to the skin can remove oils and dead skin cells from the 
surface and aid in the release of trapped hairs, with the 
potential to improve the efficiency of the cutting process. 
Shaving preparation formulas typically contain a high per¬ 
centage of water, which provides an additional hydration 
source for the hair and skin. Finally, shaving preparations 
are usually based on surfactants and contain other ingredi¬ 
ents such as oils or polymers. For reasons already noted 
hydrating hair and skin is important for the shaving process, 
but hydration increases the coefficient of friction for an 
object sliding across the skin's surface [14]. The surfactants, 
oils, and polymers in shave gels can reduce friction to 
improve razor glide, provide a cushion between the blade 
and skin, and improve cutting efficiency. 


161 














HYGIENE PRODUCTS Personal Care Products 


Table 21.1 Summary of some differences between males and females related to hair characteristics and blade shaving behaviors and attitudes. 


Male Female 


Onset of shaving behavior 

Most males begin shaving between the 
ages of 14 and 15 

Most females begin shaving between the 
ages of 11 and 13 

Body areas shaved 

Most male shaving occurs on the face 
and neck areas. The average male shaves 
an area of -300cm 2 

Female shaving is focused on the leg and 
underarm areas. The average female shaves 
an area of -2700cm 2 

Relative hair density 

Higher hair density. On average the male 
face has 500 hair follicles per cm 2 [7] 

Lower hair density. On average the leg and 
axillae have 60-65 hair follicles per cm 2 [7] 

Hair growth pattern 

Hair on the face tends to grow in 
multiple directions 

Hair on the legs tends to grow in the same 
direction, but hair in the underarm area 
grows in multiple directions 

Location where shaving occurs 

Males tend to shave at the bathroom sink 

Females tend to shave in the shower or bath 

Attitudes towards shaving 

Males tend to view shaving as a skill 

Females tend to view shaving as a chore 


Equipment and technique are also important for an 
optimum shaving experience. The razor should be in good 
condition with a sharp blade. A dull blade will not cut the 
hair cleanly and will pull the hair, increasing discomfort and 
the likelihood of nicks and cuts. Shaving in the direction of 
hair growth with a light pressure is recommended to reduce 
pulling, at least for the first few strokes. These preliminary 
strokes can be followed up with strokes against the grain if 
additional hair removal is needed. On the face, feeling the 
beard with the hand can help identify hair growing patterns 
and guide stroke direction. Skin on some areas of the body, 
such as the underarms, has a naturally uneven or very 
pliable surface. Pulling the skin taut on these areas during 
shaving can improve the efficiency of the hair removal 
process and reduce nicking or cutting. In all cases the razor 
should be rinsed often to keep the blade surface clean. 

Some situations may require extra care during the shaving 
process. For example, pseudofolliculitis barbae (PFB) is a 
condition that affects individuals with very tightly curled 
hair, such as those who are of African descent. In PFB hairs 
may grow parallel to, rather than out from, the skin's surface 
and in some cases the tip of the hair curves back and grows 
into the surface of the skin, causing inflammation. Individuals 
prone to developing PFB should thoroughly hydrate the hair 
before shaving, liberally use a shaving preparation and if 
blade shaving, shave daily with a sharp razor. 

Following the shave, skin should be thoroughly rinsed 
with water to remove all traces of shaving preparation, 
because these products are generally surfactant-based and 
leaving surfactant in contact with the skin can induce or 
exacerbate irritation. Rinsing with cool water can have a 
soothing effect on the skin. Applying a moisturizer can also 
have a soothing effect and will hydrate the skin to help 


prevent dryness. Moisturizers can also speed the barrier 
repair process and thus help to mitigate any stratum corneum 
damage that might result from shaving. 

These steps apply generally to blade shaving needs for 
both sexes. However, there are differences between males 
and females in terms of hair characteristics and blade shaving 
behaviors and attitudes. As a result, razors for females are 
often designed to accommodate body specific needs. Some 
of these differences are summarized in Table 21.1. 

References 

1 Richards R, Meharg, G. (1991) Cosmetic and Medical Electrolysis 
and Temporary Hair Removal: A Practice Manual and Reference Guide. 
Medric Ltd, Toronto. 

2 Saitoh M, Uzuka M, Sakamoto M. (1969) Rates of hair growth. 
Adv Biol Skin 9, 183-201. 

3 Tolgyesi E, Coble DW, Fang FS, Kairinen EO. (1983) A compara¬ 
tive study of beard and scalp hair. J Soc Cosmet Chem 34, 361-82. 

4 Thozhur SM, Crocombe AD, Smith AP, Cowley K, Mullier M. 
(2007) Cutting characteristics of beard hair. J Mater Sci 42, 
8725-37. 

5 Deem D, Rieger MM. (1976) Observations on the cutting of 
beard hair. J Soc Cosmet Chem 27, 579-92. 

6 Michael-Titus A, Revest P, Shortland P, Britton R. (2007) The 
Nervous System: Basic Science and Clinical Conditions. Elsevier Health 
Sciences, UK. 

7 Bhaktaviziam C, Mescon H, Matoltsy AG. (1963) Shaving. I. 
Study of skin and shavings. Arch Dermatol 88, 874-9. 

8 Hollander J, Casselman EJ. (1937) Factors involved in satisfac¬ 
tory shaving. JAMA 109, 95. 

9 Terry J. (1991) Materials and design in Gillette razors. Mater Des 
12, 277-81. 

10 Marti VPJ, Lee RS, Moore AE, Paterson SE, Watkinson A, 
Rawlings AV. (2003) Effect of shaving on axillary stratum 
corneum. Int J Cosmet Sci 25, 193-8. 


162 





21. Blade shaving 


11 Ya-Xian Z, Suetake T, Tagami H. (1999) Number of cell layers of 
the stratum corneum in normal skin: relationship to the ana¬ 
tomical location on the body, age, sex and physical parameters. 
Arch Dermatol Res 291, 555-9. 

12 Auriol F, Vaillant L, Machet L, Diridollou S, Lorette G. (1993) 
Effects of short-term hydration on skin extensibility. Acta Derm 
Venereol [Stockh] 73, 344-7. 


13 Visscher MO, Tolia GT, Wickett RR, Hoath SB. (2003) Effect of 
soaking and natural moisturizing factor on stratum corneum 
water-handling properties. J Cosmet Sci 54, 289-300. 

14 Highley DR, Coomey M, DenBeste M, Wolfram LJ. (1977) 
Frictional properties of skin. J Invest Dermatol 69, 303-5. 


163 



Section III 
Adornment 





Part 1: Colored Facial Cosmetics 


Chapter 22: Facial foundation 

Sylvie Guichard and Veronique Roulier 

L'Oreal Recherche, Chevilly-Larue, France 


BASIC CONCEPTS 

• Facial foundation places a pigment over the skin surface to camouflage underlying defects in color and contour. 

• Facial foundations must be developed to match all ethnicities and facial needs. 

• New optic technologies have allowed modern facial foundations to create a flawless facial appearance more effectively. 

• Facial foundations impact skin health because they are worn daily for an extended period. 


Introduction 

Complexion makeup is anything but a trifling subject. The 
practice is deeply rooted in human history. It has evolved 
along with civilizations, fashions, scientific knowledge, and 
technologies to meet the various expectations depending on 
mood, nature, culture, and skin color. A prime stage to 
beautifying the face, complexion makeup creates the 
"canvas" on which coloring materials are placed. Women 
consider it as a tool to even skin color, modify skin color, or 
contribute to smoothing out the skin surface. To fulfill these 
different objectives, substances extracted from nature took 
on various forms over time until formulation experts devel¬ 
oped a complex category of cosmetics including emulsions, 
poured compacts, and both compact and loose powders. 
These developments have improved the field of skin care 
providing radiance, wear, and sensory effects. 

It remains a challenge to adequately satisfy the varying 
makeup requirements of women from different ethnic 
origins, who do not apply products in the same way and do 
not share the same diverse canons of beauty. It is therefore 
necessary to gain a thorough understanding of the world's 
skin colors. 

Finally, as a product intended to be in intimate contact 
with the skin, facial foundations must meet the most strenu¬ 
ous demands of quality and safety. This has motivated evalu¬ 
ation teams to develop methods for assessing product 
performance. 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Complexion makeup - an ancient practice 

Modifying one's self-appearance by adding color and orna¬ 
ment to the skin of the face and body skin is hardly a recent 
trend [1-3]. From Paleolithic times, man has decorated 
himself with body paint and tattoos for various ritual activi¬ 
ties. In the Niaux Cavern (Ariege, France), the cave of 
Cougnac (Lot, France), and the Magdalenian Galleries of le 
Mas d'Azil (Ariege), the past ages have left evidence of these 
practices. Along with the flint tools in the Magdalenian 
Galleries at le Mas d'Azil ochre nodules were found that look 
like "sticks of makeup" as well as grinding instruments, jars, 
spatulas, and needle-like "rods" 8-1 lcm long, tapered at 
one end and spatula-shaped on the other end, suitable for 
applying body paint. 

From the earliest of ancient civilizations, there are cos¬ 
metic recipes containing a variety of ingredients which are 
often closer to magic than to rational chemistry, aimed par¬ 
ticularly at modifying the complexion. Usually used exclu¬ 
sively by high dignitaries, cosmetics were intended to whiten 
the complexion. 

Ancient Mesopotamia (2500 bc) 

The queen and the princes of Ur used cosmetics consisting 
of a mixture of mineral pigments based on Talak (from 
which the word "talc" is derived). Nowadays such cosmetics 
are still commonly used in some parts of the Middle East. 

Ancient Egypt (3rd millennium bc) 

The priests used plaster to cover their faces. It was also desir¬ 
able for women to exhibit very white skin without blem¬ 
ishes, as these were indications of a privileged life of leisure. 


167 









ADORNMENT Colored Facial Cosmetics 


The complexion was whitened with mixtures of plaster, 
calcium carbonate, tin oxide, ground pearls, and lead 
carbonate (ceruse) mixed with animal grease, waxes, and 
natural resins. Evidence of the complexity of the ancient 
recipes has been determined by chemical analyses carried 
out jointly by the Centre National de la Recherche 
Scientifique, L'Oreal's Recherche department, the Research 
Laboratory of the Museums of France, and the European 
Synchrotron Radiation Facility on the content of cosmetic 
flasks found in archeologic excavations [4]. The earliest 
cosmetic formulary is attributed to Cleopatra - "Cleopatrae 
gyneciarum libri ." 

Ancient Greece 

In Ancient Greece, the white, matte complexion symbolizing 
purity was obtained through generous application of plaster, 
chalk, kaolin ( gypsos ), and ceruse (psimythion) , but Plato was 
already denouncing the harmfulness of these cosmetics. 

Ancient Rome 

Ancient Rome raised the use of makeup to the level of an 
art form. In addition to cosmetics that enhance the beauty 
of face and body, cosmetics were applied to improve appear¬ 
ance and hide flaws, notably those caused by the aging 
process. 

Women of the upper classes "coated" their face with 
complex mixtures with recipes reported in Ovid's Cosmetics 
or in Pliny the Elder's Natural History. For instance, hulled 
barley, powdered stag antlers, narcissus bulbs, spelt, gum, 
and honey were the components of a mixture to make the 
face shiny. Dried crocodile excrement, ceruse, vegetal 
extracts, as well as lanolin or suint (also known as oesype) 
were used to whiten the complexion. 

Recently, an analysis was made of an ointment can, chris¬ 
tened Londinium , discovered in London when excavating a 
temple dated at the middle of the 2nd century ad. It con¬ 
tained glucose-based polymers, starch, and tin oxide. The 
white appearance of the cream reflects a certain level of 
technological refinement [5]. 

From the Middle Ages to the 19th century 

In Europe, from the Middle Ages up to the middle of the 
20th century, good breeding and good manners were associ¬ 
ated with a white complexion. In the Middle Ages, makeup 
was based on water, roses, and flour, which did not prevent 
ceruse from making a strong comeback in the Renaissance. 
It was then subsequently mixed with arsenic and mercury 
sublimates to give the complexion a fine silver hue. 

Toxic effects of these cosmetics, however, was beginning 
to worry the authorities. In 1779, following the onset of a 
number of serious cases, the manufacture of "foundation 
bases" was placed under the control of the Societe Royale 
de Medicine, which had just been set up in 1778. The toxic 
components were then removed. This measure seems to 


have made them disappear from the market, but it was not 
until 1915 that the use of ceruse was officially prohibited. 

In 1873, Ludwig Leichner, a singer at the Berlin Opera, 
sought a way to preserve his skin tone by creating his 
own foundation base from natural pigments. In 1883, 
Alexandre Napoleon Bourjois devised the first dry or pastel 
foundation. Bourjois was about to launch his first dry blush, 
Pastel Joue. 

With the birth of the cosmetics industry, products were 
widely distributed. Modern manufacturing techniques with 
production on an industrial scale coupled with the begin¬ 
ning of mass consumer use started at the beginning of the 
20th century. 

20th century: the industrial era and diversification 

In the 20th century, fashionable powders for the complex¬ 
ion became more sophisticated [6,7]. Market choice extended 
with the launch of new brands such as Gemey, Caron, and 
Elizabeth Arden. 

The 1930s saw the development of trademarks such as 
Helena Rubinstein and Max Factor created by professional 
movie and Hollywood makeup artists. The products were 
suited to the requirements of the movie studios. Extremely 
opaque, tinted with gaudy colors, they were compact and 
difficult to apply. After the success of Max Factor's Pancake 
and Panstick cosmetics, use of the word "makeup" became 
widespread. Initiated by Chanel in 1936, the fashion in 
Europe and the USA began to switch from white to a tanned 
complexion. 

Even though women were more inclined to wear cosmet¬ 
ics, makeup was still not part of everyday life. Pancake 
makeup, a mixture of stearate, lanolin, and dry powders, 
was not easy to apply. Technical advances gradually made 
products more practical. The box of loose powder was 
equipped with a sieve in 1937 (Caron). In 1940, Lancome 
launched Discoteint, a creamy version of its compact. Coty 
micronized its powder (Air Spun) in 1948. Yet, it was not 
until the 1950s that a real boom occurred in the number of 
products on the market. Compact makeup was made avail¬ 
able in creamy form; foundation became a fluid cream 
(Gemey, Teint Clair Fluide, 1954). It was the start of a great 
diversification of formulations: fluids, dry or creamy com¬ 
pacts, sticks, and powders. Makeup became multifaceted, 
with more sophisticated effects, including moisturizing, pro¬ 
tection from damaging environmental factors, and other 
skincare properties in addition to providing color. 

Since then, complexion makeup has followed the con¬ 
tinuous changes in regulations and advances in biologic 
knowledge, especially in the area of skin physiology. Over 
the last decades, it has benefitted from technologic progress 
in the field of raw materials, as well as from enhanced 
understanding and gains in optics and physical chemistry. 
Finally, makeup was enriched with the diversity of cultures 
from all over the world prompted by globalization. The 


168 


22. Facial foundation 


beginning of the 21st century opens a new era of visual 
effects, sensory factors, and multiculturalism. 


Formulation diversity 

Women expect foundations to effect a veritable transforma¬ 
tion that hides surface imperfections, blemishs, discolora¬ 
tions, and wrinkles, while enhancing a dull complexion and 
making shiny skin more satiny. Whereas making up the eyes 
and the lips is generally done playfully, the complexion 
receives more attention. It is in this area that women display 
their greatest expertise and are the most demanding. Women 
have high expectations for their foundation including: 

• Guaranteed evenness and concealment of flaws; 

• Hiding of wrinkles and pores; 

• Good adherence to the skin; 

• Matting of lustrous skin; 

• Excellent wear all day long; 

• Unaltered color over time; 

• Pleasant, easy application; and 

• Appropriate for sensitive skin. 

Variety of formulations 

In order to satisfy diverse demands, a large number of 
products types and forms have been developed (Figure 
22 . 1 ): 

• Fluid foundations; 

• Compact, easy-to-carry foundations with adjustable 
effects; and 

• Powders to be used alone or in combination with a fluid 
foundation. 

Fluid foundations: emulsions 

Fluid foundations include both oil-in-water (O/W) and 
water-in-oil (W/O) emulsions. Until the 1990s, most foun- 



Figure 22.1 Diversity of textures: from fluid emulsion to paste 
dispersion. 


dations were O/W emulsions. Generally intended for mixed 
to oily skin, they are characterized by: 

• Very rapid drying, which can complicate even 
application; 

• Poor coverage; 

• Reduced wear; 

• Appropriate for mixed to oily skin with their external 
aqueous continuous phase, which makes them feel fresh on 
the skin. 

In the 1990s, the first W/O formulations revolutionized 
the foundation market. The external oil continuous phase 
gives textures with longer drying times more suitable for 
perfect product application. The progressive coating of pig¬ 
ments has improved their dispersion in the oil phase and 
helped to stabilize the emulsion. 

Throughout the years, the oil phase has been diversified 
mainly as a result of introducing silicone oils, first in con¬ 
ventional then in volatile forms. Silicone oils have dramati¬ 
cally changed the cosmetic attributes of facial foundation. 
Foundation no longer has to be spread evenly over the face. 
Its slickness makes it slide on the skin evenly with a single 
stroke without caking. The use of volatile oils, siliconated or 
carbonated, gave rise to the design of long-lasting founda¬ 
tions. As the volatile phase evaporates, the tinted film con¬ 
centrates on the skin. Adhering during drying on the skin 
surface, the tinted film withstands friction and does not stain 
clothes. 

Thus, the "non-transfer" facial foundation was born. 

In the 21 st century, combining volatile oils with different 
volatilities will lead to novel cosmetic attributes; the oily 
phase gradually evaporates accompanying finger strokes 
during application. Today, 90% of the foundations on the 
market are water/silicone/oil emulsions. Over the past few 
years, the chemistry of the emulsifying agents have also 
expanded as new functionalized emulsifiers become avail¬ 
able. Either endowed with moisturizing effects or able to 
enhance optical properties, they contribute to the comfort 
and the performance of facial foundations. 

Compact foundations 

Compact foundations are made up of waxes and oils in 
which powders and pigment phases are dispersed under 
heat, but compact foundations can be greasy, heavy, and 
streaky. The more recent use of esters and siliconated oils 
has made it possible to lighten the texture and improve 
application qualities. Volatile oils also help the facial founda¬ 
tion film remain unaltered for a longer time and provide 
long-lasting coverage. Compact foundations display the 
advantage of being adjustable with a sponge, which is ideal 
for concealing localized defects. Packaging the foundation in 
compact cases makes it practical for touching up during the 
day. 

Waterpacts are a special compact type that contain water. 
They consist of W/O or O/W emulsions rich in waxes that 


169 




ADORNMENT Colored Facial Cosmetics 


are poured into the compact under heat. The water content 
makes it necessary to use waterproof packaging. These solid 
emulsions are difficult to manufacture and preserve, but 
they have the huge advantage of making the compact fresh 
as well as practical in use. 

Compacts can also be packaged as sticks for more precise 
and localized strokes, such as around the eyes. 

Powders 

Compact powders are distinct from loose powders as they 
represent the "portable to go" version of loose powders. 
They are composed of fillers and pigments. A binder con¬ 
taining 10% oils and grease ensures the compact powder 
particle cohesion, while also providing comfort and ease of 
application. To make a high-quality powder a suitable milling 
procedure must be used in order to disperse the pigments 
finely and evenly throughout the powder phase. 

Loose powders 

A loose powder is characterized by weak particle cohesion. 
It does not contain binder or may contain just enough to 
provide a degree of cohesion that controls the final product 
volatility. Loose powders are generally applied with a puff, 
but manufacturers are developing tricks for easy application 
by using more finely tuned application brushes. Unlike with 
a puff, the powder does not scatter. 

Compact powders 

There are different kinds of compact powders: 

• Finishing powders provide sheer coverage and are used 
for touch-up during the day. They are usually applied with 
a sponge over a foundation to mask facial shine. The fillers 
used in these powders tend to be organic, because they are 
more transparent. They also have the advantage of absorb¬ 
ing sebum while still leaving a natural look. The formulation 
challenge is to find a good balance between texture quality 
and the ease in placing the proper amount of powder on the 
applicator. 

• Powder foundations are compact or loose powders whose 
covering power is equivalent to that of a foundation (i.e. 
better than a finishing powder). They can be used instead 
of foundation, for instance by women who dislike fluid 
textures. The loose powder version known as mineral 
makeup is currently enjoying considerable success. 

• Two-way cakes, which are available in compact form, can 
be used either wet or dry. This kind of powder is popular 
with Japanese women. Using it dry gives the same kind of 
makeup as a powder foundation, while using it wet gives 
more even coverage. This dual usage requires the vast 
majority of the fillers to be hydrophobic. Treated fillers, 
coated with silicone oils that cannot be wetted, are mostly 
used. In this way, the compact remains unaltered after 
contact with water and does not cake. These two-way cakes 



Figure 22.2 The four iron oxides used in foundations. 


are formulated to provide fuller coverage than powder foun¬ 
dations. They give a very matte appearance that will not 
wear off in hot, humid conditions such as in the Asiatic 
climate. 

The main drawback of all powders is a certain discomfort 
relative to foundation, mainly because of the absence of any 
moisturizing effect (Table 22.1). 

Color creation 

At the core of foundation formulations there is a combina¬ 
tion of colored powders that must be: 

• As finely dispersed as possible with optimal stability; and 

• Able to create a natural-looking tinted film once smeared 
over the skin. 

To achieve this end, the formulator has available various 
colorants that comply with the different cosmetics legisla¬ 
tions (positive lists) and are thus certified to be harmless, 
chemically pure, and microbiologically clean. These are 
inorganic pigments such as metallic oxides - yellow, red, and 
black iron oxides - to which colored and uncolored pearls 
can be added to give a lustrous effect. To brighten founda¬ 
tions (especially the darkest ones) blue pigment can be sub¬ 
stituted for black. 

For improved pigment dispersion and formula stability, 
the process of pigment coating has gradually become the 
standard. In water/silicone emulsions, a silicone coating is 
most frequently used. Coating with an amino acid aims at 
developing products for sensitive skin. 

Pigments and coverage 

The amount of titanium oxide pigment in the product is an 
indication of its ability to cover skin flaws (i.e. the level of 
coverage provided). A foundation is characterized by theo¬ 
retical coverage on a scale from 7 (natural effect) to 50 


170 



22. Facial foundation 


Table 22.1 Products categories overview. 

Skin type target 

Formulations characteristics 

Name of category 

Main objectives 

All types of skin but 
adapted to Asian routine 

Uncolored formulations 

To be applied under foundation 

Foundation base 

Application: Lasting effect - spreadability 
Moisturizing effect - matt finish 

All types of skin 

Weakly colored 

Tinted creams 

Strong skincare attributes 

All types of skin 

Weakly colored but pearly 

Bronzers 

Highlighters 

Healthy "glow" effect, suntan color 

All types of skin 

Greens, purples, blues, apricot 

Complexion correctors 

Correction of discoloration (red spots by 
green tints) 

Complexion freshener (apricot - blue) 

All types of skin 

Low to full coverage 

Fluid foundations 

Wear - matt finish 

Antiaging - radiance 

Normal to oily skin 

Low to full coverage 

Compacted powders, such 
as two-way cakes 
(adapted to Asian routine) 

Matt finish - complexion evenness 

Normal to dry skin 

Medium to full coverage 

Compact foundation 

Evenness - adjustability of the result. 
Comfort - mobility 

Normal to oily skin 

Weak to medium coverage 

Waterpacts (poured 
emulsions) 

Same properties as compacts, plus 
freshness and hydrosoluble actives 

Eye contour 

Medium to full coverage 

Concealers 

Hides dark circles under the eyes 

All types of skin 

Transparent to opaque (mineral 
makeup) 

Loose powders 

Matt finish and adhesion - evenness 


(corrective makeup). However, this ignores the optical prop¬ 
erties of the product, which may also be able to mask skin 
defects through a soft focus effect [8]. It also does not take 
into account the influence of texture, which will determine 
how transparent or opaque the colored deposit is according 
to the ability of the product to spread evenly as a thin layer 
over the skin. 

Importance of fillers 

Fillers are all the non-pigment powders introduced in the 
product to provide: 

• Covering power; 

• The ability to absorb sebum and sweat so as to make the 
skin velvety and fix the color to the skin; 

• Fineness and smoothness, which enhances cosmetic qual¬ 
ities of the textures; and 

• Spreadability, which makes application easier. 

Both form and chemical nature govern the final qualities of 
fillers (Figures 22.3a-c). Talc is an example of a spreadable, 
lamellar powder that is widely used for its extreme softness 
and absorbing power. Kaolin, starches, and calcium carbon¬ 
ate used to be widely employed but they have now been 
superseded by: 


• Different varieties of silica, sometimes porous forms; 

• Polymers such as nylon and polymethylmethacrylate 
(PMMA); and 

• Mica platelets that can also be coated. 

Not only are these powders essential to the basic properties 
of a product, but they also contribute to its optical properties. 
Transparent or opaque, lustrous, matte, or soft focus, they 
help to achieve the desired finish on the skin. 


Facial foundation application 

Most women usually apply their facial foundation first when 
applying cosmetics. They may choose to modify their com¬ 
plexion color or make it more glowing and even without 
changing the color. Whatever effect is desired, makeup is 
used to recreate an ideal of color and finish peculiar to each 
individual according to ethnic and cultural practices. It must 
also be adapted to suit the woman's routine: application of 
a single product, use over a base or under a powder, stroked 
on by finger or by sponge. 

There is a great diversity in the use of complexion makeup. 
The formulator must address several issues. Being familiar 


171 






ADORNMENT Colored Facial Cosmetics 





(a) (b) (c) 

Figure 22.3 Shape variety of fillers (a-c). 


with the various skin color characteristics is a primary req¬ 
uisite for recreating the shades that closely match the ethnic 
origin of the user. For any given product, this is a necessary 
prerequisite for creating a range of shades that will likely 
satisfy the women throughout the world, whether Caucasian, 
Hispanic, African, or Asian. 

A large study carried out on a widely representative panel 
demonstrated significant differences in the colorimetric 
characteristics of skin color of six ethnic groups living in nine 
different countries [9,10]. The recorded measurements 
enabled the definition of a wide color space showing the 
various color spectra typical of each ethnic group's skin color 
mesh and overlap (Figure 22.4). 

Further studies showed that the variety of makeup rou¬ 
tines reflected the ethnic origin and cultural heritage which 
determines whether a woman feels positive toward her 
natural skin color. For many women, skin color is a major 
factor in their cultural identity. Complexion makeup is the 
easiest way to achieve even skin color by erasing surface 
color variations or correcting color unevenness. Some 
women wish to appear more deeply "tanned" than their 
natural color. This behavior is commonly found in Caucasian 
and Hispanic women. Japanese women, however, desire 
their makeup to give them a lighter complexion (Figure 
22.5) [10]. 

The formulator works within this defined scope to develop 
shades matching natural skin colors. To meet women's 
expectations, it is necessary to analyze how women self- 
perceive their complexion. By identifying skin colors within 
a definite color range and precisely identifying the makeup 
habits of women over the world, it is now possible to for¬ 
mulate a variety of shades that match up with the wishes of 
all women. 


Emphasis on quality, safety and 
confirmed performance 

Complexion makeup creates an intimate relationship 
between the skin and a complex formulation that is left on 
for hours. Before being marketed, every product has to 


undergo a battery of tests to confirm its safety and perform¬ 
ance. There are several steps in this process. 

Design stage 

The formulator must ensure high quality ingredients are 
used by defining specifications and analytical controls and 
carrying out screening for the non-toxicity of the ingredients 
with in vitro tests on reconstructed skin models. Each raw 
material used must be cleared for safety and have a proper 
toxicologic dossier. 

Formulation stage 

It is necessary to: 

• Evaluate stability by subjecting products to thermal cycles 
to accelerate aging. 

• Confirm the level of microbiologic preservation of the 
formulas using challenge tests. The selected method of pres¬ 
ervation and the nature of the preservatives depend on the 
technology involved (powder emulsion, anhydrous 
compact). The risk of microbiologic contamination increases 
with the water content. It also depends on the packaging; a 
pump bottle provides better protection than a jar. 

• Check it is harmless through using alternate methods: 
in vitro testing and including tests run on reconstructed skin 
model, e.g. (EpiSkin®, L'Oreal Episkin SNC, Lyon, France); 
clinical tests (simple patch test [SPT] and repeated patch test 
[RPT]); and, finally, user tests under dermatologic controls, 
carried out on the product's targeted skin types, particularly 
on sensitive skins and using wide ranging, representative 
panels. Use testing under ophthalmologic controls is carried 
out systematically on products intended to mask under-eye 
rings. 

Performance stage 

The performance of the product must be studied to ensure 
that it complies with consumer wishes and to obtain an 
unbiased opinion on advertising claims and consumer 
complaints. Sensorial analysis tests provide qualitative and 
quantitative assessments of a product's features by a trained 
panel of experts, as well as by untutored panels performing 
the tests under the formula's normal user conditions. 


172 






22. Facial foundation 



Figure 22.4 (a) The color of the 
forehead was measured using a 
spectroradiometer inside a 
Chromasphere™. (b) The volunteer 
placed her face into the Chromasphere. 
A standardized camera was used to 
acquire pictures of the face, (c) A 
spectroradiometer measured the 
reflectance of forehead in the visible 
field 400-700 nm every 4nm. The 
recorded spectrum was expressed in the 
CIE 1976 standard colorimetric space 
L*C*h D65/10 0 where each color is 
described through three coordinates that 
reflect perception by human eye. h, Hue 
angle (angular coordinate); C* f chroma 
(radius coordinate); L* f lightness (z axis). 


Reflectance 

0 . 8 “i- 


0.7 

0.6 

0.5 

0.4 

0.3 

0.2 

0.1 

0 


350 


Wavelength (nm) 


400 


450 


500 


550 


600 


650 


700 


750 



L*=62.7 

C*=27.0 

h=58.8 


(c) 


Additionally, a complexion product can be tested with the 
conventional methods used for skincare cosmetics: 

• Measurement of moisturizing effects using SkinChip® 
(L'Oreal, Chevilly-Larue, France) or Corneometer® (Courage 
& Khazaka, Koln, Germany); 

• Effects on skin firmness with using the Dermal Torque 
Meter® (Dia-Stron Ltd, Andover, UK); 

• Image analysis on skin imprints or, even better, projection 
of light fringes involving no contact with skin (i.e. skin in 
real conditions with makeup as applied) to assess antiwrin¬ 
kle performance. 


Also specific tests: 

• Color appraisal using the Chromasphere® (L'Oreal, 
Chevilly-Larue, Lrance): the difference in the color of the 
skin before and after applying makeup quantifies the 
improvement in color evenness and change in color effect. 
Moreover, it makes it possible to monitor both. As a result, 
the manufacturer can claim that its makeup effects last a 
given number of hours. 

• Evaluation of the matt finish with a suitable 
device (Samba® [Bossa Nova Technologies, Venice, 
CA, USA]). 


(b) 


173 




























ADORNMENT Colored Facial Cosmetics 


80 


70 


60 


50 


40 


30 



Figure 22.5 The worldwide skin color space depicted in (h, L*) and split in six groups of skin tones that reflect the color diversity. 


Conclusions and prospects 

Beauty is diverse. Textures, tones, matte or lustrous results, 
play time, and sensoriality must all come together to give 
a woman a simple means to recreate her ideal complexion. 
Complexion makeup products today benefit from knowl¬ 
edge of physical chemistry, resulting in better understand¬ 
ing of the relationships between chemical composition, 
texture, and application behavior. Facial foundations 
benefit from technologic advances in optics, which has 
generated formulations that are sheer, glowing, matte, able 
to provide soft focus concealment of flaws, while simulta¬ 
neously giving shades that mirror the natural hues of the 
skin. 

Complexion makeup products have been expanded to 
deliver multisensory effects and address ethnic diversity 
issues. From simple emulsions applied by finger, facial foun¬ 
dations have evolved into mousses, creamy compacts, and 
soft powders that can be applied by brush or sponge, and 
layered. Facial foundations contribute to beauty of the face 
respecting the women's own skin, but also addressing their 


culture and ethic diversity [11,12]. New forms, new optical 
effects, and new application methods will permit users to 
attain their ideal complexion irrespective of origin or own 
canons of beauty. 

References 

1 Claude C. (2006) Histoire du maquillage du teint: une vision 
croisee des cultures, des modes et des evolutions technologiques. 
These pour l'obtention du Diplome d'Etat de Docteur en 
Pharmacie Faculte Paris V. 

2 Groning K. (1997) La Peinture du Corps. Arthaud Editions. 

3 Griind F. (2003) Le Corps et le Sacre. Editions du Chene Hachette 
Livre. 

4 Walter P, Martinetto P, Tsoucaris G, Breniaux P, Lefebvre MA, 
Richard G, et al. (1999) Making make-up in ancient Egypte. 
Nature 397, 483-4. 

5 Evershed RP, Berstan R, Grew F, Copley MS, Charmant AJH, 
Barham E, et al. (2004) Formulation of a Roman cosmetic. 
Nature 432, 35-6. 

6 Chanine N, Deprund MC, De La Forest F, et al. (1996) 100 Ans 
de Beaute. Atlas Editions. 

7 Pawin H, Verschoore M. (2001) Maquillage du Teint du Visage. 
Paris: Encyclopedic Medicale Chirurgicale, Cosmetologie 


174 
























22. Facial foundation 


Dermatologie Esthetique Editions Scientifiques et Medicales 
Elsevier. 

8 Takayoshi I, Miyoji O. (2002) Appealing the technical function 
of the optical characteristic foundation from the view point of 
marketing. Fragrance J 30, 59-63. 

9 Caisey L, Grangeat F, Lemasson A , Talabot J, Voirin A. (2004) 
Skin color and make-up strategies of women from different 
ethnic groups. Int J Cosmet Sci 28, 427-37. 

10 Baras D, Caisey L. Skin, lips and lashes of different skins of color: 
typology and make-up strategies. In AP Kelly and SC Taylor, 


Dermatology for Skin of Color. McGraw-Hill, Berkshire, UK, 
pp. 541-9. 

11 Mulhern R, Fieldman G, Hussey T, Leveque JL, Pineau P. (2003) 
Do cosmetics enhance female Caucasian facial attractiveness? Int 
J Cosmet Sci 25, 199-205. 

12 Korichi R, Pelle-de-Queral D, Gazano G, Aubert A. (2008) Why 
women use make-up: implication of psychological traits in 
make-up functions. J Cosmet Sci 59, 127-37. 


175 


Chapter 23: Camouflage techniques 

Anne Bouloc 

Cosmetique Active International, Asnieres, France 


BASIC CONCEPTS 

• Camouflage makeup is used to cover facial defects of contour and color. 

• Camouflage makeup must be artistically applied to achieve an optimal result. 

• Camouflage techniques can improve quality of life. 

• Camouflage therapists can train patients in the proper application techniques for cosmetics. 


Introduction 

Camouflage techniques can be helpful in patients who do 
not achieve complete or immediately attractive results from 
dermatologic therapy. Because appearance is one of the 
pivotal factors influencing social interactions, facial blem¬ 
ishes and disfigurements are a psychosocial burden in 
affected patients leading to low self-esteem and poor body 
image. Camouflage makeup can normalize the appearance 
of skin and improve quality of life. Training in camouflage 
techniques is essential because the application is different 
from regular foundations. This chapter discusses the use of 
camouflage cosmetics. 


Definitions 

Camouflage cosmetics were introduced more than 50 years 
ago to improve the appearance of World War II pilots who 
had sustained burns. The products provided an opaque 
cover over the damaged skin areas. Modern high quality 
camouflage products provide a excellent coverage, but with 
a more natural appearance (Figure 23.1). 

There are several brands of camouflage makeup on the 
market. They aim to conceal skin discoloration and scars and 
to impart a natural, normal appearance. Camouflage prod¬ 
ucts differ from makeup products purchased over the 
counter. They contain up to 25% more pigment, as well as 
fillers endowed with optical properties. Camouflage makeups 
are waterproof and designed to cover and mask a problem, 
but must be mixed to match the patient's skin tone. The 
goals of camouflage cosmetics are to provide [1]: 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


1 Color: Camouflage makeup must match all skin tones as 
it should blend into the color of the area on the face it is 
intended to cover evenly. 

2 Opacity: Camouflage makeup must conceal all types of 
skin discoloration, yielding as natural and normal an appear¬ 
ance as possible. 

3 Waterproof: Camouflage makeup must be rain and sweat- 
resistant, remaining unaltered with athletics (e.g. 
swimming). 

4 Holding power: Camouflage makeup must adhere to skin 
without sliding off. 

5 Longer wear: Camouflage makeup must provide the assur¬ 
ance of long wear with easy reapplication, if necessary. 

6 Ease of application: Camouflage makeup must be easy to 
apply. Too many steps and color applications may create 
patient confusion. 

There are several different types of camouflage 
cosmetics: 

1 Full concealment: A method referring to complete coverage 
of the damaged skin and extending beyond the boundaries 
of the injured area. High coverage foundation creams or 
cover creams should be used for full concealment. 

2 Pigment blending: A method that involves selection of a 
cover cream that matches the color of patient's 
foundation. 

3 Subtle coverage: A light application of foundation cream 
that conceals only moderately. 

Contouring is used to minimize areas of hypertrophy or 
atrophy present in facial scars, using highlighting or shading 
to create the illusion of smoothness. 


Camouflage makeup application 
procedures 

It is important to remember that camouflage makeup is most 
effective when applied over skin with color abnormalities or 


176 








23. Camouflage techniques 


Figure 23.1 Ideal corrective makeup: a compromise 
between coverage and cosmetic qualities. After Sylvie 
Guichard, L'Oreal Recherche. 


High level 
of coverage 


30- 


20 - 


# High coverage potential 

# Difficult to apply 

# No natural result 

# Heaviness 


10 - 

Low level 
of coverage 


IDEAL CORRECTIVE MAKE-UP 
High coverage potential 

♦ Easy to apply 

# Natural result 


♦ Less coverage potential 

♦ Good playtime 

♦ Comfortable texture 


> 


Low 

cosmetic 

qualities 


Excellent 

cosmetic 

qualities 


discoloration. The size of the defect is immaterial, because it 
is as easy to cover a large blemish as a smaller one. However, 
the camouflage of texture abnormalities is more challenging. 
Rough scars are more difficult to conceal than smooth scars 
because unevenness is exaggerated after camouflaging [2]. 

This section of the chapter presents the steps necessary to 
complete a camouflage makeup application procedure for a 
given patient. First, patients should be asked about prior 
experience in attempting to camouflage their lesions with 
or without medical makeup. If they have no experience, the 
necessary steps should be discussed in detail. Second, the 
patient's skin should be cleansed with a product selected 
according to patient's skin type. For an optimal camouflage 
result, the skin should be well exfoliated and moisturized. If 
using a camouflage product without sun protection factor 
(SPF) protection, a sunscreen-containing moisturizer should 
be selected otherwise a bland moisturizer can be used. 

Third, the camouflage product must be selected to match 
the patient's skin. The camouflage therapist should identify 
the underlying tones that contribute to skin color: haemo¬ 
globin produces red, keratin produces yellow, and melanin 
produces brown [3]. Thinner skin possesses more red tones 
while thicker skin appears more yellow. For this reason, it 
is almost impossible to mimic natural skin color with only 
one shade. 

Fourth, the camouflage therapist must understand color. 
There are three color coordinates: hue, value, and 
intensity. 

1 Hue is the coordinate for the pure spectrum colors com¬ 
monly referred to as "color name" - red, orange, yellow, 
blue, green, violet - which appear in the hue circle or 
rainbow. Each different hue is a different reflected wave¬ 
length of light. White light splitting up through a prism has 
seven hues: red, orange, yellow, green, blue, indigo, and 
violet. 

2 Value is defined as the relative lightness or darkness of a 
color. Adding white to a hue produces a high value color. 


often called a tint. Adding black to a hue produces a low 
value color, often called a shade. 

3 Intensity , also called chroma or saturation, refers to the 
brightness of a color. A color is at full intensity when not 
mixed with black or white - a pure hue. The intensity of a 
color can be altered, making it duller or more neutral by 
adding gray to the color. 

Matching a color from one manufacturer to another one 
is a very difficult procedure because of the variety of shades 
that can be produced by combining various colors and the 
tints of the color that can be made by varying the amount 
of white. Judgment of color should always be made on the 
skin and never in the container because what seems to be 
the same shade may appear quite different on the skin. 

The use of neutralizers in camouflaging is somewhat con¬ 
troversial. Some experts think it is possible to neutralize 
undesirable skin discoloration [2]. For example, green 
undertoner neutralizes a red complexion and lavender 
undertoner negates a yellow complexion. Other authors 
think that makeup undertoners do nothing but create a third 
color [4]. They consider that when two colors are mixed, 
the result is a third color. Mixing opposite colors on the color 
wheel (e.g. green and red or yellow and purple) will result 
in an unattractive gray-brownish color that must be con¬ 
cealed with a color that matches the skin, which adds an 
extra step and thickness to the makeup. 

For contouring, several products have to be applied. 
Hypertrophic scars appear lighter than surrounding skin, 
and have to be camouflaged applying a darker product than 
to surrounding skin. Atrophic scars, however, appear darker 
than surrounding skin, and have to be corrected using 
lighter product. 

Once the shades have been selected, the camouflage ther¬ 
apist should apply them to the back of the hand as a painter 
uses a palette to warm and soften the product (Figure 
23.2a,b). The warm skin makes the product more malleable 
so it will apply more easily. Camouflage products are best 


177 













ADORNMENT Colored Facial Cosmetics 





(a) 



(d) (e) (f) 

Figure 23.2 Camouflage makeup technique, (a) Remove a small amount of the corrective makeup, (b) Warm the product on the back of the hand, (c) 
Apply over the imperfection to be covered, (d) Blend in round the edges, (e) Generously apply the powder, (f) Remove any surplus with a brush. 


applied with a sponge in a patting motion but can also be 
applied with the fingertips (Figure 23.2c). The patting 
motion applies the product to the surface of the skin and 
does not clog pores, which allows the skin to retain its 
natural characteristics. Distinct borders are eliminated by 
blending the edges (Figure 23.2d). 

A camouflage product often is not used over the entire 
face like a regular facial foundation, but the surrounding 
skin must be matched as closely as possible. Patients have 
to be reminded that skin color on the hands does not really 
correspond to skin color of the face. The application is gener¬ 
ally followed up with an application of powder which sets 
and waterproofs the camouflage product (Figure 23.2e,f). 
The setting powder used should be translucent so that the 
camouflage product does not change color. For patients with 
very dry skin, it is not necessary to use a powder as the oils 
are quickly absorbed into the skin. 

Many patients may prefer using only one shade even 
when the color match is not perfect. Men may not wish to 
mix colors. It might be of interest to show the patient the 


coverage with one shade and the coverage using more than 
one shade while demonstrating that color blending is rela¬ 
tively easy and worthwhile. 

For men, common skin flaws must be reproduced in order 
to prevent a "mask-like" appearance [3]. Beard stubble can 
be recreated by using different sponges and a brown or black 
pigment that mimics surface irregularities. Other colored 
powdered blushes can be used on the cheeks to simulate the 
natural glow of youth and around the eyes and mouth to 
attract the attention on other parts of the face [6]. Pictures 
should be taken before and after the application to docu¬ 
ment the cosmetic results. 

Finally, the cosmetics must be removed each evening prior 
to bed. Removing camouflage makeup is more difficult than 
regular makeup. Alcohol or acetone-based removers are too 
irritating for sensitive skin, thus it is better to use water- 
soluble cream-type makeup remover. The remover is applied 
generously to emulsify the makeup followed by wiping with 
cotton pads. The face is then rinsed with tepid water and 
patted dry [7]. 


178 





23. Camouflage techniques 


Other camouflage therapies 

A few other options than camouflage makeup therapies 
have been suggested. Dihydroxyacetone, the main ingredi¬ 
ent in self-tanning creams, has been proposed for camou¬ 
flaging in patients with vitiligo [8]. It may be a cheap, safe, 
and effective alternative especially for the hands and the feet 
as cover creams are waterproof but not rubproof. 

Medical tatooing under local anesthesia has also been 
tried to create the appearance of hair in hairless areas [9]. 
The pigment used is made of ferrous oxide, glycerol, and 
alcohol. A test on a small area should be performed to evalu¬ 
ate the outcome. The needle should be introduced into the 
dermis similarly to the natural hair pattern of the patient. 


Medical indications for 
camouflage makeup 

There are various medical indications for camouflage 
makeup. The lesion requiring camouflage can be permanent 
or temporary. The best results are obtained with macules, 
but papules, nodules, or scars can also be camouflaged. 
Macular lesions for camouflaging include pigmentary disor¬ 
ders such as vitiligo (Figure 23.3), chloasma (Figure 23.4), 
lentigenes, postinflammatory hypopigmentation or hyper¬ 
pigmentation (Figure 23.3); hypervascular disorders such as 
telangiectasia (Figure 23.6) and angioma (Figure 23.7); and 
tattoos. Papulonodular lesions for camouflaging include 
discoid lupus, acne, dermatosis papulosa nigra, and facial 
scars. 

After a graft for oncologic surgery, or for other postsurgical 
scars, there may be variation in pigmentation and/or relief 
and corrective cosmetics may be of interest. Depending on 


the skin's ability to heal, camouflage therapy can be applied 
7-10 days after most surgical procedures. However, the pre¬ 
mature use of makeup following epidermal damage may 
cause a secondary infection or tattooing effect. 

There may be transient injuries or lesions of the skin that 
can be camouflaged with makeup. An injury may produce 
hematoma and oedema that should be concealed for occu¬ 
pational reason or social event. Corrective makeup can also 
be used after medical procedures such as laser resurfacing, 
peels, and microdermabrasion to camouflage erythema. 
After filler injections, redness may also appear. Laser hair 
removal will induce temporary redness, but following some 
lasers the skin may become purpuric. Camouflage makeup 
optimizes the patient's postprocedure appearance. Indeed, if 
the patient knows he or she will be red, he or she will 
require an appointment at the end of the day or of the week. 
With corrective makeup, patients are able to go back straight 
to work. Similarly, after filler or botulinum toxin injections, 
hematomas may appear which can be camouflaged with 
corrective makeup. 


Beginning a camouflage clinic 

It is important to offer patients camouflaging makeup 
knowledge [6]. In general, the dermatologist will delegate 
this activity to a staff member. Many physicians find that a 
camouflage therapist can bring an added value to the prac¬ 
tice by enhancing patient recovery. 

The room for teaching camouflaging techniques should 
contain a table with a mirror and fluorescent bulbs to 
provide adequate light. A chair should be placed in the room 
tall enough to allow the camouflage therapist to stand. 
Several camouflage products should be available in various 
shades to match the different skin colors. 


Figure 23.3 Perioribital 
hyperpigmentation: (a) before and (b) 
after camouflage. 



179 












(bi) 



(aii) 

Figure 23.4 Vitiligo: (a) (i & ii) before and (b) (i & ii) after camouflage. 



(bii) 



Figure 23.5 Melasma: (a) before and 
(b) after camouflage. 


(a) 

















23. Camouflage techniques 



Figure 23.6 Vascular malformation: 

(a) (i & ii) before and (b) (i & ii) after 

camouflage. ( a 'i) (bii) 


The camouflage therapist 

In the USA, camouflage therapists are state-licensed and 
medically trained skincare professionals, with both clinical 
knowledge and therapeutic skill [5]. They do not treat 
patients but educate them by providing information on the 
best way to go about applying camouflage makeup. In other 
countries of the world such a degree does not exist. 
Camouflage therapists should obtain appropriate training 


and education. They should be trained to select and apply 
cosmetics beyond the application of standard cosmetics. 
Their training should include the study of facial anatomy, 
highlighting and contouring techniques, and prosthetic 
makeup techniques similar to those used in the stage and 
motion picture industry. 

The camouflage therapist should be a good communicator 
to teach patients how to apply various products, which the 
patient can easily reproduce without assistance. Camouflage 
therapists should be genuinely interested in the patient's 


181 










ADORNMENT Colored Facial Cosmetics 



Figure 23.7 Telangiectasia: (a) before and (b) after camouflage. 


well-being. Therefore, they should be mature enough to 
work with people who have a severely damaged 
appearance. 

The camouflage therapist must record the patient's history 
and identify needs based on the patient's perception of the 
problems. Because of the clinical knowledge and personal 
qualities required, a trained nurse would be an ideal cam¬ 
ouflage therapist [7,10]. 

The camouflage therapist can design a cosmetic treatment 
plan. During the interview four issues should be addressed 
[5]: 

1 The ability of the patient to follow simple instructions. 

2 The patient's social activities and job environment. 

3 The patient's prior makeup experience. 

4 The financial status of the patient. 


Camouflage makeup and quality of life 

Psychosocial aspects of skin disease has important implica¬ 
tions for optimal management of patients. The presence of 
abnormal visible skin lesions may result in significant psy¬ 
chologic impairment. Health-related quality of life (QOL) is 
a measurement method to describe physical, social, and 



psychologic well-being and to assess the burden of disease 
on daily living. Several general measures have been devel¬ 
oped [11]. Surprisingly, women who used facial foundation 
reported a poorer QOL than those who did not. This was 
interpreted to mean that more severely impacted patients 
are more likely to hide the disorder using camouflage cos¬ 
metics, albeit inadequately. Yet, wearing makeup may 
improve appearance and looking better translates into 
feeling better. Those who feel better show signs of higher 
self-esteem. 

Many studies have been performed in order to demon¬ 
strate the effects of corrective makeup on patients' QOL 
[12-14] and remove misconceptions that the use of cosmet¬ 
ics can be tedious and difficult for ordinary people. A wide 
range of facial blemishes and disfigurements such as pig¬ 
mentary disorders, vascular disorders, scars, acne, rosacea, 
lupus, lichen sclerosus, and keratosis pilaris have been 
included in these studies. QOL questionnaires were com¬ 
pleted before the first application and after applying correc¬ 
tive makeup. Results show that corrective cosmetics are 
well-tolerated and patients report high satisfaction rates. 
There is an immediate improvement in skin appearance and 
no significant adverse effects. Corrective cosmetics rapidly 
improve QOL, which persists with continued use. There was 


(b) 


182 







23. Camouflage techniques 


no difference in QOL according to the type of facial disfig¬ 
urement or the size of the affected area. Not only were 
patients improved with pigmentary or vascular disorders, 
but also with scars. 

Camouflage therapy can help patients cope with skin dis¬ 
orders that affect appearance. The cosmetics can be used 
long-term without difficulty. Camouflage therapy is of great 
help to patients who cannot be medically improved. 


Conclusions 

Camouflage techniques help affected patients cope with the 
psychologic implications of facial blemishes or disfigure¬ 
ments. Covering visible signs of the disease minimizes 
stigmatization. Today's high quality camouflage products 
provide excellent good coverage with a natural appearance. 
Many physicians find that a camouflage therapist can bring 
an added value to the practice by enhancing patient 
recovery. 

References 

1 Westmore MG. (2001) Camouflage and make-up preparations. 
Dermatol Clin 19 , 406-12. 

2 Draelos ZK. (1993) Cosmetic camouflaging techniques. Cutis 52 , 
362-4. 


3 LeRoy L. (2000) Camouflage therapy. Dermatol Nurs 12 , 
415-6. 

4 Westmore MG. (1991) Make-up as an adjunct and aid to the 
practice of dermatology. Dermatol Clin 9 , 81-8. 

5 Rayner VL. (1995) Camouflage therapy. Dermatol Clin 13 , 
467-72. 

6 Deshayes R (2008) Le maquillage medical pour une meilleure 
qualite de vie des patients. Ann Dermatol Venereol 135 , S208-10. 

7 Rayner VL. (2000) Cosmetic rehabilitation. Dermatol Nurs 12 , 
267-71. 

8 Rajatanavin N, Suwanachote S, Kulkllakarn S. (2008) 
Dihydroxyacetone: a safe camouflaging option in vitiligo. Int J 
Dermatol 47 , 402-6. 

9 Tsur H, Kapkan HY. (1993) Camouflaging hairless areas on the 
male face by artistic tattoo. Dermatol Nurs 5 , 118-20. 

10 McConochie L, Pearson E. (2006) Development of a nurse-led 
skin camouflage clinic. Nurs Stand 20 , 74-8. 

11 Balkrishnan R, McMichael AJ, Hu JY, et al. (2006) Correlates 
of health-related quality of life in women with severe facial 
blemishes. Int J Dermatol 45 , 111-5. 

12 Boehncke WH, Ochsendorf F, Paeslack I, Kaufmann R, Zollner 
TM. (2002) Decorative cosmetics improve the quality of life in 
patients with disfiguring diseases. Eur J Dermatol 12 , 577-80. 

13 Holme SA, Beattie PE, Fleming CJ. (2002) Cosmetic camouflage 
advice improves quality of life. Br J Dermatol 147 , 946-9. 

14 Balkrishnan R, McMichael AJ, Hu JY, et al. (2005) Corrective 
cosmetics are effective for women with facial pigmentary disor¬ 
ders. Cutis 75 , 181-7. 


183 



Chapter 24: Lips and lipsticks 

Catherine Heusele, Herve Cantin, and Frederic Bonte 

LVMH Recherche, Saint Jean de Braye, France 


BASIC CONCEPTS 

• The lips possess a complex anatomy consisting of mucosa and skin. 

• Lipsticks are designed to enhance the appearance of the lips. 

• Lipstick is an anhydrous paste of oils and waxes in which pigments are dispensed along with other coloring agents. 


Introduction 

Lip makeup is an essential element in seduction and women 
frequently use lipsticks to make their faces more attractive. 
The lips are muscular membranous folds surrounding the 
anterior part of the mouth. This tissue is both mucosa and 
skin and has a complex anatomy. Labial tissue has a dense 
population of sensory receptors, is very sensitive to environ¬ 
mental stress, can present pigmentation defects, and is modi¬ 
fied during aging. Lipstick formulations are most widely 
used to enhance the beauty of lips and to add a touch of 
glamour to women's makeup. The lipstick that we know 
today is a makeup product composed of anhydrous pastes 
such as oils and waxes in which are dispersed pigments and 
other coloring agents designed to accentuate the complexion 
of the lips. This chapter draws together our knowledge of 
the biology of this special tissue, and gives detailed informa¬ 
tion on the formulation elements of lipsticks. 


Lip anatomy 

The lips are muscular membranous folds surrounding the 
anterior part of the mouth. The area of contact between 
the two lips is called the stomium and forms the labial 
aperture. The external surfaces of the lips are covered by 
skin, with its hair follicles, sebaceous glands, and sweat 
glands; the inner surface is covered by the labial mucosa, a 
non-stratified, non-keratinized epithelium bearing salivary 
glands. The transitional zone between these two epithelia is 
the red vermilion border of the lips (Figure 24.1). It has 
neither hair follicles nor salivary glands, but sebaceous 
glands are present in about 50% of adults [1]. The red area 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


is also keratinized, with rete ridges more marked than in the 
neighboring cutaneous zone. 

Several studies have identified an intermediate area 
between the vermilion zone and the mucosa that does not 
contain a cutaneous annex; it is covered by a stratified epi¬ 
thelium that lacks a stratum granulosum but does have a 
thick parakeratin surface layer. This intermediate zone 
increases with age [2-4]. 

The deeper region of this soft tissue forming the lips is 
made up of a layer of striated muscle, the orbicularis orbis 
muscle, and loose connective tissue. The muscle makes a 
hooked curve towards the exterior at the edge of the ver¬ 
milion area which gives the lips their shape. 

Immediately above the transition between the skin and 
the vermilion zone is the Cupidon arch, a mucocutaneous 
ridge, also called a white roll, or the white skin roll. Its physi¬ 
cal appearance and lighter color seem to be essentially 
caused by the configuration of the underlying muscle [5]. 
This region is rich in fine, unpigmented, "vellous" hairs that 
may influence the appearance of this zone. 

The lips have great tactile sensitivity. Labial tissue has a 
dense population of sensory receptors, including Meissner 
corpuscles, Merkel cells, and free nerve endings. The sensi¬ 
tivity of the lips is somewhere between that of the tongue 
and the fingertips [6]. 

Labial epidermis 

The epidermis of the vermilion region is twice as thick 
(180 pm) as the adjacent skin [4,7,8]. It still has the markers 
of cutaneous epidermis differentiation, even though it has 
fewer keratinized layers than the skin [9]. Barrett et al. [4] 
found that the distribution of cytokeratins (CK) differed 
from that of the intermediate zone, with a loss of the skin 
cytokeratins CK1 and CK10 and the presence of the mucosal 
cytokeratins CK4, CK13, and CK19. CK5 and CK14 were 
still present in the basal layer and occasionally in the supra- 
basal layer. CK8, CK18, and CK20 were found only in 
Merkel cells. Involucrin was present in all the zones, but its 


184 







24. Lips and lipsticks 


oc 

LU 

Q 

DC 


o 


CD 


DC 

LU 

> 



MUCOSA 


laris orbis 
muscle 


vessels 


Follicles 


Lamina propria 


SKIN “—-Epidermis 


Figure 24.1 Lip histology. 


restricted distribution in the stratum granulosum of the skin 
extended to the stratum spinosum and the parabasal kerati- 
nocytes of the lip zone and the mucosa. Loricrin, profilag- 
grin, and filaggrin were found in the stratum granulosum of 
the orthokeratinized zones but not after the junction 
between the vermilion zone and the intermediate zone. 

The corneocytes in the mucosa are flat, smooth cells. In 
contrast, most of the corneocytes on the surface of the ver¬ 
milion border are seen to have microvilli on all their internal 
surfaces when examined under the high power microscope 
[10]. These projections are rarely seen on the corneocytes 
of the adjacent skin [11]. The cell turnover of the epidermis 
of the vermilion border seems to be more rapid than that of 
the adjacent skin cells. The vermilion border also appears to 
lose water three times as fast as the cheeks and to have only 
one-third the conductance. Thus, the lips function as a 
barrier but their capacity to retain water is much poorer than 
that of facial skin [1]. 

Hikima et al. [11] showed that the surface of the lips, like 
the surface of the skin, has cathepsin D-like activity and 
chymotrypsin-like activity. These enzymes are involved in 
the hydrolysis of corneodesmosomes, and hence in the 
release of corneocytes from the skin surface. 

Like the skin, the vermilion border epithelium contains 
melanocytes and there is melanin in the cytoplasm of basal 
cells [4]. However, as the melanin pigmentation is light and 
associated with reduced keratinization, the color of the 
hemoglobin is seen more clearly. There are also Langerhans 
cells in this zone [8]. Cruchley etal. [12] used immunodetec¬ 
tion of CD la to show that there were more Langerhans cells 
per unit area of the lips than in abdominal skin. 


Sallette et al. [13] recently showed that there is more 
neuropeptide-type neurotransmitter in the epidermis of the 
lips than in the eyelids, which seems to indicate that the lips 
are better innervated. 

Lip dermis and lamina propria 

The epithelium of the vermilion border lies on a layer of 
connective tissue, which ensures the continuity of the cuta¬ 
neous dermis and the lamina propria. This tissue is com¬ 
posed of collagen fibers and a network of elastic fibers. 

There is a thin layer of fatty tissue between the muscle 
and the dermis in the cutaneous part of the lips with many 
attachments between the muscle and the skin [14]. The 
deep part of the lamina propria of the mucosa lies above the 
hypodermis of the subcutaneous zone. The invaginations at 
the junction between the epithelium and the connective 
tissue of the vermilion border are higher than those of the 
skin [13]. These papillae contain blood capillaries. The capil¬ 
lary loops in the vermilion border are higher than those of 
the skin, which accentuates the red color of the lips because 
of the hemoglobin in them [16]. 

The lymph drainage of the red border is not uniform; it 
flows towards the cutaneous system on the external side of 
the lips and towards the mucosal system on the inner side 

[17] . 

Lip topology 

The description of lip topology first interested legal medicine 
because each individual has a different organization, much 
like fingerprints. The study of lip prints is called cheiloscopy. 
The development of kiss-proof lipsticks led legal medicine to 
develop protocols for revealing latent prints at a crime scene 

[18] . Lip prints can be classified in several ways and their 
distributions in populations have been quantified [19-22]. 

Sensitivity of lips to the environment 

As the lips have little cornified tissue or melanin they are 
very sensitive to chemical, physical, or microbial damage. 
Their prolonged exposure to sunlight, particularly for fair¬ 
skinned people, may lead to the appearance of actinic cheili¬ 
tis and even spinocellular carcinoma [23]. Pogoda and 
Preston-Martin [24] suggested that frequent applications of 
sunscreen can have a positive protective effect. Smoking has 
also been found to be a major risk factor for lip cancers. 

Aging of the lips 

The esthetic consequences of aging of the superficial lip 
tissues (sagging, distension, and ptosis) are aggravated by 
changes in the shape of the bone and dental infrastructure 
and the aging of the underlying muscles and adipose tissue. 
The orientation of the labial aperture changes with a droop¬ 
ing of the lateral commissures: from a concave curve in 
newborns and children to a horizontal line in adults, and 
then to an inverted curve in the elderly. In profile, the lips, 


185 





ADORNMENT Colored Facial Cosmetics 


particularly the lower lip, recede with age. The upper lip 
becomes lower and enlarged [3,22]. Tissues become less 
extensible and elastic because of repeated mechanical 
stresses and the weakening of the orbicularis orbis muscle 
with age [3,23]. 

The vermilion border becomes larger, longer, and thicker 
at the corners of the mouth [2]. While wrinkles develop in 
the skin around the lips with age, the outline of the lips 
themselves becomes sunken [22]. The depth and organiza¬ 
tion of the lips varies greatly from one person to another 
and some young people have deep furrows. Both the spatial 
resolution and the tactile sensitivity of the lips decrease with 
age [3,6,23,26]. There may also be histologic signs of solar 
elastosis. The superficial microcirculatory network (both 
papillary and mucosal) may become smaller and less dense 
(reticular and mucosal), together with an apparent thinning 
of the lips in older people who have lost their teeth [15]. 

Cosmetic surgery can be used to "refresh" and to fill the 
tissue to rejuvenate the lips. This might involve reducing the 
upper lip or recovering the shape of a young lip by a series 
of interventions to reinforce the shape and projection of the 
lips and restructure the Cupid's bow, better define the lip 
outline, and lift the corners of the mouth. This surgery is 
accompanied by a rejuvenation of the perioral region, 
including removal of peribuccal wrinkles, peeling, laser 
resurfacing, and dermabrasion [27-30]. 

Lip plumpness and cheilitis 

Cheilitis can be caused by a cold or dry environment, 
repeated pressure on the lips - as it can develop in players 
of wind instruments - or by defective dental work. It can 
also occur in people taking oral retinoids, or from a lack of 
dietary vitamin B 12 (riboflavin), B 6 (pyridoxine), nicotinic 
acid, folic acid, or iron [31]. 

Hikima et al. [11] reported that the corneocytes at the 
edges of dried out lips become flattened and their surface 
area increased. This suggests that the turnover of these cells 
is slowed in dried out lips. The degree of visible dryness is 
also correlated with a reduction in cathepsin D, one of the 
enzymes involved in desquamation, but the chymotrypsin- 
like activity remains unchanged. 

The upper lip seems to dry out less than the lower lip as 
it is less exposed. While the hydration measured by the 
capacitance does not seem to change with age, the loss of 
water via the lips decreases [25]. Clinically assessed drying 
out increases with age [22]. 

Defects of lip pigmentation 

Pigmentation defects, particularly ephelides and lentigos, 
may also occur. The lips of some populations, like those from 
Thailand, may become dark because of the accumulation of 
melanin in the basal layer of the epidermis without any 
increase in the number of melanocytes [32]. This disorder 
may be congenital, caused by smoking, or an allergic reac¬ 


tion to a topical compound. Smoking can also increase pig¬ 
mentation of the buccal mucosa in darker-skinned people 
(Africans, Asians, Indians) [33]. 


Lipsticks 

Lipstick, a symbol of feminine beauty and sensuality and 
a method of attracting attention, has a very long history. 
The red color and bloom (lively, plump) of the lips was 
first accentuated in the ancient world. Today, a woman 
uses lipstick to highlight her individuality, character, and 
seductive capacity and to underline her smile [34]. It is 
everything but an empty gesture; it reflects the image that 
the woman has of herself and what she wants to project in 
society. 

In the 18th century, people distinguished between the red 
coloring used for the lips and the rouge used for the cheeks. 
Many rather toxic substances have been used in the past. 
The red coloring material used can be of animal, vegetable, 
or mineral origin. It could be obtained from the cochineal 
beetle imported from Mexico, the purple dye extracted from 
molluscs, red sandalwood from Brazil, or the orcanette root. 
The minerals most frequently used were lead oxide 
(minium), mercuric sulfate (cinnabar), and antimony. 

The popularity of lipstick exploded in the 20th century 
with the use of lip makeup based on a colored paste made 
from grapes and sold in little jars. These were deep colors. 
The mouth became much fuller with the arrival and spread 
of talking movies in the 1930s. The first "indelible" or "kiss- 
proof" lipstick was the lipstick Rouge Baiser sold by the 
French chemist Paul Baudecroux in 1927. Red, pouting lips 
became all the rage in the 1950s, while in the 1990s lip gloss 
or brilliant was produced as a paste rather than a stick. 

Lipstick formulation 

The lipstick that we know today is a makeup product com¬ 
posed of anhydrous pastes in which are dispersed pigments 
and other coloring agents designed to accentuate the com¬ 
plexion of the lips. It is formed into a stick by pouring the 
hot material into a mould. A classic lipstick formula is: 

• Wax (about 15%) which is solid at room temperature. It 
provides hardness and creaminess when applied; 

• Waxy paste (20%) helps lubricate the lipstick after 
application; 

• Oil (30%) for dispersing the pigments; 

• Texturing agents (about 10%) to improve the texture; 

• Coloring agents, pigments, and/or pearls (20%) to give 
color; 

• Preserving agents and antioxidants (1%) to stabilize the 
formulation; 

• Perfume (1%); 

• Active ingredients including UV filters to improve long¬ 
term benefit. 


186 



24. Lips and lipsticks 


Table 24.1 Waxes 


Origin 

Wax 

Properties 

Source 

Appearance 

Animal 

Beeswax 

Composed of fatty acids and alcohols 
Thickener 

Bees 

Relatively solid, give a 
lustrous appearance 

Plant 

Carnuba wax 

Harder than bees wax 

Very slightly acid, but brittle 

Often used mixed with bees wax 

From the leaves of the carnuba 
palm (Brazil) 

Relatively hard, and give a 
lustrous appearance 


Candelilla wax 

Very hard wax 

From the candelilla plant 

Matte appearance 

Mineral 

Paraffin 

Ozokerite 

Non-stick 

Non-polar 

White, fairly transparent and odorless 

Paraffin is obtained from oil refining 

More malleable 


Table 24.2 Waxy pastes. 

Origin 

Name 

Properties 

Source 

Appearance 

Synthetic 

Polybutene 

Adherence 

Brilliance 

Extremely hydrophobic 

Synthesis from ethylene 

Very viscous transparent, 
viscous liquid 

Synthetic 

Methyl hydrogenated rosinate 





Waxes 

The wax may be of vegetable, animal, or synthetic origin. 
They are solid at room temperature and must be melted for 
use. They create a crystalline network within the formula¬ 
tion that gives the lipstick its shape. The wax is chosen to 
give the stick a suitable hardness so that it does not break 
during application. They also give the lipstick a rather matte 
appearance (Table 24.1). 

Lipsticks are currently made using specific fractions of wax 
that provide specific fusion points. These refined fractions 
are whiter and more odorless than the original waxes, which 
were a complex mixture of natural lipids. 

Waxy pastes 

They are called pastes because they are semi-solid forms 
of wax at room temperature (Table 24.2). They contribute 
to the cosmetic function of the lipstick by helping to keep 
the color on the lips. They can do this because they are 
sticky and because their fusion point is close to the 
temperature of the lips, thus enabling the stick to melt 
during application. 

Oils 

These hydrophobic liquids are solvents for the coloring 
agents that allow them to diffuse so as to develop their color. 
The oils provide comfort, lubrication during application, and 
contribute greatly to the cosmetic effect. They may also 


Table 24.3 Oils 

Name 

Properties 

Source 

Appearance 

Di isostearylmalate 

Emollient 

Not oxidized 

Colorless 

Odorless 

Synthetic 

Colorless liquid 

Trimethylolpropane 

Tri isostearate 

Emollient 

Comfort 

Synthetic 

Colorless, 
viscous liquid 

Polyglyceryl-2 

Tri isostearate 

Emollient 

Comfort 

Dispersant 

Synthetic 

Transparent pale 
yellow liquid 


provide brilliance and subtlety (Table 24.3). Castor oil has 
been used for many years but is now less often utilized. It 
has excellent pigment-dispersing properties because of its 
polarity; its main inconvenience is its unpleasant taste and 
odor (caused by oxidation). It is gradually being replaced by 
stable, odorless, fatty acid esters. 

Texturing agents 

These components can be very different; they provide mois¬ 
turizing, brightness, and subtlety. For example, polyamide 


187 











ADORNMENT Colored Facial Cosmetics 


Table 24.4 Pigments and coloring agents. 


Component 

Origin 

Titanium (IV) oxide - mica 

Mineral 

Ferrous oxide (II) 

Mineral 

Ferric oxide (III) 

Mineral 

DC Red 33 

Organic 

DC Red 27 

Organic 

DC Red 21 

Organic 

DC Red 7 

Organic 

DC Red 6 

Organic 

DC Red 28 

Organic 

DC Red 30 

Organic 


powders bring softness, silica beads provide subtlety and a 
matte finish, titanium dioxide flakes give a soft-focus effect, 
while bismuth oxychloride gives a satin, shimmering effect. 

Pigments 

Pigments are synthetic substances or of mineral origin. 
They are fine powders when dry and are used because 
they are very opaque and have great coloring properties 
(Table 24.4). 

The solid powders are suspended and dispersed in oil. The 
covering property of a lipstick depends on its pigment 
content; these pigments can hide the underlying lip color. 
International regulations strictly limit the use of pigments. 
Only a restricted number can be used on the face because 
of the risk of ingestion. The pearly and metallic effects are 
obtained with composite materials, often multilayered. 
These are interference pigments because they create long 
wavelength interference patterns in natural light. Holographic 
effects may be obtained by liquid crystals (cholesterol deriv¬ 
atives) or multilayer plastic slabs (terephthalates). 

Antioxidants and preserving agents 

The most frequently used antioxidants are the (3-carotenes 
(provitamins A), ascorbic acid, and tocopherol, which are all 
powerful, natural antioxidants. The preserving agents are 
used to control bacterial proliferation. There are few pre¬ 
serving agents (phenoxyethanol mainly) in anhydrous prod¬ 
ucts such as lipsticks. 

Perfume 

Perfume provides the desired smell to the lipstick. It is gener¬ 
ally used as an oil-based concentrate that is miscible with 
the other oils in the formulation. 


Active ingredients 

These are used to provide their specific properties to the 
finished product and often permit claims of antiaging or 
moisturizing. They must be included at the considered con¬ 
centration to be effective. Vitamin A, as (3-carotene, vitamin 
E (tocopherol), and vitamin C are classically used in lipstick. 
Sunscreen can be used to protect the lips against UV rays for 
an antiaging quality. 

Lip glosses and brilliances 

A lip brilliance is a makeup product that generally has low 
covering qualities but reflects light and gives the lips a shiny 
appearance. A brilliant lipstick has a gloss effect. So, by 
extension, the term lip gloss includes lip brilliants. 

Lip glosses nourish the lips and give them a light, wonder¬ 
fully supple appearance and a long-lasting sparkle. Their 
crystalline effect is brought about by their ultra-brilliant, 
transparent base. They may be used over a lipstick to give a 
new sparkle to the lipstick color, or simply provide the lips 
with a very pure, superfine color. Its formulation differs 
from that of lipstick only in the quantity and nature of the 
components classically used in lipsticks. 

Lip glosses are frequently sold in small flasks and are 
applied with a special applicator. They are not applied 
directly to the lips, so they do not need to have a solid struc¬ 
ture like a lipstick. The wax content is lower and the content 
of waxy paste higher. 


Conclusions 

Lipsticks and lip glosses are essential to a women's makeup, 
and have a key role in the affirmation of her personality 
and well-being. These skin surface products - thanks to 
their simple formula that contains a limited number of 
constituents - are usually well accepted and adverse reac¬ 
tions are very rare. 

Pink, purple, even blue, the colors follow the fashion 
trends, and, most of the time, they are coordinated with 
clothes and nail polishes. The shapes and textures that 
women appreciate remain quite classic. Indeed, if raw mate¬ 
rials are constantly evolving, cosmetic regulations world¬ 
wide lay down some new restrictions to the manufacturers 
of the beauty sector. Nevertheless, these regulatory evolu¬ 
tions still allow the creation of ever more innovative and 
qualitative products. 

References 

1 Kobayashi H, Tagami H. (2005) Functional properties of the 
surface of the vermilion border of the lips are distinct from those 
of the facial skin. Br J Dermatol 150, 563-7. 

2 Binnie WH, Lehner T. (1970) Histology of the muco-cutaneous 
junction at the corner of the human mouth. Arch Oral Biol 15, 
777-86. 


188 






24. Lips and lipsticks 


3 Fogel ML, Stranc MR (1984) Lip function: a study of normal lip 
parameters. Br J Plast Surg 37, 542-9. 

4 Barrett AW, Morgan M, Nwaeze G, et al. (2005) The differentia¬ 
tion profile of the epithelium of the human lip. Arch Oral Biol 
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5 Mulliken JM, Pensler JM, Kozakewich HPW. (1993) The 
anatomy of vermilion bow in normal and cleft lip. Plast Reconstr 
Surg 92, 395-404. 

6 Stevens JC, Choo KK. (1996) Spatial acuity of the body surface 
over the life span. Somatosens Mot Res 13, 153-66. 

7 Lafranchi HE, de Rey BM. (1978) Comparative morphometric 
analysis of vermilion border epithelium and lip epidermis. 
Acta Anat 101, 187-91. 

8 Heilman E. (1987) Histology of the mucocutaneous junctions 
and the oral cavity. Clin Dermatol 5, 10-6. 

9 Kuffer R. (1982) Pathologie de la muqueuse buccale et des 
levres. Encyelopedie Medicochirurgicale (Paris), Dermatologie, 12830 
A10. 

10 Muto H, Yoshioka I. (1980) Relation between superficial fine 
structure and function of lips. Acta Dermatol Kyoto Engl Ed 75, 
11 - 20 . 

11 Hikima R, Igarashi S, Ikeda N, et al (2004) Development of lip 
treatment on the basis of desquamation mechanism. IFSCC 
Magazine 7, 3-10. 

12 Cruchley AT, Williams DM, Farthing PM, et al. (1994) Langerhans 
cell density in normal human oral mucosa and skin: relationship 
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55-9. 

13 Sallette J, Al Sayed N, Laboureau J, Adem C, Soussaline F, 
Breton L. (2006) Neuropeptide Y may be involved in human lip 
keratinocytes modulation. J Invest Dermatol 126, suppl 3, si 3. 

14 Choquet P, Sick H, Constantinesco A. (1999) Ex vivo high resolu¬ 
tion MR imaging of the human lip with a dedicated low field 
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15 Wolfram-Gabel R, Sick H. (2000) Microvascularisation of lips in 
ageing edentulous subjects. Surg Radiol Anat 22, 283-7. 

16 Iwai I, Yamashita T, Ochiai N, et al. (2003) Can daily-use lipstick 
make lips more fresh and healthy? A new lipstick containg a- 
glucosyl hesperidin can remove the dull-color from lips. 22nd 
IFSCC Conference, pp. 162-77. 

17 Ricbourg B. (2002) Vascularisation des levres. Ann Chir Plast 
Esthet 47, 346-56. 

18 Ball J. (2002) The current status of lip prints and their use for 
identification. J Forensic Odontostomatol 20, 43-6. 


19 Sivapathasundharam B, Prakash PA, Sivakumar G. (2001) Lip 
prints (cheiloscopy). Indian J Dent Res 12, 234-7. 

20 Hirth L, Gottsche H, Goedde HW. (1975) Lips print: variability 
and genetics. Humangenetik 30, 47-62. 

21 Hirth L, Goedde HW. (1977). Variability and formal genetics of 
labial grooves. Anthrop Anz 36, 51-7. 

22 Leveque JL, Goubanova E. (2004) Influence of age on the lips 
and perioral skin. Dermatology 208, 307-14. 

23 Calvalcante ASR, Anbinder AL, Carvalho YR. (2008) Actinic 
cheilitis: clinical and histological features. J Oral Maxillofac Surg 
66 , 498-503. 

24 Pogoda JM, Preston-Martin S. (1996) Solar radiation, lip protec¬ 
tion, and lip cancer risk in Los Angeles County women 
(California, United States). Cancer Causes Control 7, 458-63. 

25 Caisey L, Gubanova E, Camus C, Lapatina N, Smetnik V, 
Leveque JL. (2008) Influence of age and hormone replacement 
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14, 220-5. 

26 Wohlert AB. (1996) Tactile perception of spatial stimuli on the 
lip surface by young and older adults. J Speech Hearing Res 39, 
1191-8. 

27 Simon E, Strieker M, Duroure F. (2002) Le vieillissement labial: 
composantes et principes therapeutiques. [The lip ageing.] Ann 
Chir Plasti Esthet 47, 556-60. 

28 Aiache AE. (1997) Rejuvenation of the perioral area. Dermatol 
Clin 15, 665-72. 

29 Guerrissi JO. (2000) Surgical treatment of the senile upper lip. 
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30 Ali MJ, Ende K, Maas CS. (2007) Perioral rejuvenation and lip 
augmentation. Facial Plast Surg Clin North Am 15, 491-500. 

31 Zugerman C. (1986) The lips: anatomy and differential diagno¬ 
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32 Kunachak S, Kunachakr S, Kunachark S, Leelaudomlipi P, 
Wongwaisatawan S. (2001) An effective treatment of dark lip 
by frequency-doubled Q-switched Nd:YAG laser. Dermatol Surg 
27, 37-40. 

33 Sarswathi TR, Kumar SN, Kavitha KM. (2003) Oral melanin 
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9-19. 


189 


Chapter 25: Eye cosmetics 

Sarah A. Vickery, Peter Wyatt, and John Gilley 

Procter & Gamble Cosmetics, Hunt Valley, MD, USA 


BASIC CONCEPTS 

• Mascara is intended to darken, thicken, and lengthen the lashes to make them more noticeable. Careful selection of mascara 
film materials and new applicator technologies are enhancing women's abilities to accentuate these characteristics quickly and 
effectively. 

• Other eyelash products, beyond mascara, such as lash perms and lash tints are becoming more prevalent and are beginning to 
gain mainstream acceptance. These new products are changing the way women think about eyelash beauty. 

• Eyeshadow is color applied to the upper eyelids that is used to add depth and dimension to the eyes, thus drawing attention to 
the eye look or eye color. 

• Eyeliner is used to outline the eyelids, serving to define the eyes and to make the eye look more bold or to give the illusion of a 
different eye shape. 

• New eye cosmetic products are being introduced that feature enhanced long wear, new applicator surfaces, novel color effects, 
sustainable natural materials, improved application, and even lash growth. 


Introduction 

This chapter gives a broad introduction to eye cosmetics. 
Mascara, eyeshadows, and eyeliners are presented along 
with the physiology of eyelashes and future trends. 


Eye cosmetic history 

Cosmetics have been used to decorate the eyes for thousands 
of years. In Ancient Egypt materials such as charcoal and 
kohl were mixed with animal fat to create ointment for 
darkening the lashes and eyelids. They used eye cosmetics 
for the same reasons that we do now: in youth to attract by 
accentuating and drawing attention to the eyes, and in age 
to preserve beauty as it starts to fade [1,2]. 

Moving forward to more modern times, in the 18th and 
19th centuries, men would condition their hair and mus¬ 
taches with a touch-up product for graying hair called 
Mascaro. This was also used in stage makeup as both an 
eyelash and brow cosmetic. In the 19th century women 
darkened their lashes with lamp black, which they could 
collect simply by holding up a plate to catch the soot above 
a lamp or candle flame. They also used cake mascara (soap, 
wax, and pigment wetted with a moistened brush) to darken 
their lashes, or they could plump their lashes with petro- 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


leum jelly. Since then a wide variety of innovations have 
changed both the way we decorate eyes and the penetration 
of these products into daily use by the majority of women 
[3]. 

The first half of the 20th century saw a range of new 
product forms emerge including liner pencils, melted wax 
dripped onto lashes, eyelash curlers, eyebrow pencils, lash 
dye, cream mascara (toothpaste style tube with brush), false 
lashes, liquid drops, and even turpentine-based waterproof 
mascara. As the century progressed, more and more women 
were using eye cosmetics, driven in part by the makeup of 
the popular actresses in the Hollywood movies and also 
because of new distribution systems, such as Maybelline's 
mail order mascara and availability at local stores. By the 
late 1930s, the majority of women applied cosmetics around 
their eyes [4]. 

In 1957, Helena Rubenstein launched the first modern 
day mascara - a tube of mascara cream with the applicator 
stored inside the tube. No longer was the mascara applicator 
separate from the mascara formulation. This efficient and 
more sanitary design took off quickly and, by the 1960s, 
became the standard form of mascara. Once this new product 
form was established, the applicator quickly changed from 
a simple grooved aluminum rod to the ubiquitous twisted 
wire brush applicator that is the predominant applicator 
today [3]. 

By the 1970s, waterproof mascaras were more appealing 
than the past turpentine-based versions because of the avail¬ 
ability of purified petroleum-based volatile solvents [4]. 
Fibers were introduced into mascaras for a "lengthening" 
benefit. Eyeshadows were available in a broad range of 


190 







25. Eye cosmetics 


matte and sparkling colors, partly because of the growth of 
iridescent pigments in the 1960s. By the 1980s and into the 
1990s, the rapidly improving performance of polymers 
resulted in more durable eye cosmetics that would glide on 
with ease and maintain their effect for hours [5]. 


Eyelash physiology 

Eyelashes are terminal hairs growing from follicles around 
the eye. Like all hair, the eyelash is a mixture of dead cells 
that have been keratinized, binding material, melanin gran¬ 
ules, and small amounts of water. The outer surface is com¬ 
prised of a series of overlapping, transparent scales called 
cuticle cells that protect the inside, called the cortex. The 
cortex contributes to the eyelash's shape, mechanical prop¬ 
erties, and color. Eyelashes vary by ethnicity and, as a result, 
can have an elliptical or circular cross-section with an 
average diameter of 60-120 pm, tapering to a fine, barely 
pigmented tip [6-8]. Figure 25.1 is a series of scanning elec¬ 
tron micrographs that show the shape, cross-section, and 
surface morphology of an eyelash. 

While hair over the body is likely there for thermal insula¬ 
tion and proximity sensation, eyelashes protect the eye from 
debris and signal the eyelid to close reflexively when some¬ 
thing is too close to the eye. Chemically, eyelashes are the 
same as scalp hair, and across ethnicities the chemistry of 
lashes is the same. Eyelashes have a substantially shorter, 
slower growth phase than scalp hair, hence their shorter 
length, and they typically last for 5-6 months before falling 
out. An active follicle, during the anagen (growth) cycle, will 
typically produce a lash at approximately 0.15mm/day, half 
the growth rate of scalp hair. If a lash if plucked from the 
hair follicle, a new hair can begin growing in as little as 8-10 
weeks [6-7,9]. 



Figure 25.1 Scanning electron microscope images of the eyelash. The 
eyelash tapers to a fine tip. The cross-section may be circular or elliptical 
(A), and the surface is composed of overlapping cuticle cells (B). 


The direction that the eyelash protrudes from the eyelid 
is based on the follicle's position in the skin. The curvature 
of the lash is derived from the shape of the follicle. As the 
lash forms inside the follicle, and the protein strands are 
bonded together, the lash shape that is formed corresponds 
to the shape of the follicle they are formed within. Eyelashes 
are arranged around the eye in a narrow band 1-2 mm wide. 
Lashes are longer (8-12mm) and more numerous (90-200) 
on the upper eyelid, while lower eyelid lashes number 30- 
100 and are typically 6-8 mm long [8]. 

There are a number of ailments to which the eyelashes 
are prone, the most common of which are listed in 
Table 25.1. 


Mascara 

Over half of women who wear cosmetics wear mascara. In 
fact, mascara is a product that women tend to be passionate 
about. When asked which cosmetic they would choose if 
they could only choose one, over 50% of women would 
choose mascara. 

Mascara is intended to darken, thicken, and lengthen the 
lashes to make them more noticeable. Through careful selec¬ 
tion of materials, mascara films can be produced to accentu¬ 
ate these characteristics. Mascara formulations can be 
roughly divided into two different types: water-resistant and 
waterproof. 


Table 25.1 Common eyelash ailments. 


Ailment 

Description 

Madarosis, or 
hypotrichosis 

Thinning, or loss, of eyelid and eyebrow hairs. 

Can be caused by aging, physical trauma, burns, 
X-ray therapy, overuse of glued false lashes, and 
trichotillomania (impulse to pull out one's hairs, 
including eyelashes) 

Stye 

A stye can be caused, among other things, from 
a bacterial infection of the eyelash follicle's 
sebaceous glands, leading to an inflammation of 
skin tissue around the eyelash follicle 

Poliosis 

Lashes losing their pigmentation with age, 
caused by less melanin granules being present in 
the lashes. Gray lashes are pigmented, just with 
less pigment than those of a younger person. 
Completely unpigmented lashes are white 

Trichiasis 

This is the abnormal growth of lashes directed 
towards the eyeball, causing irritation and 
possibly leading to infection 


191 












ADORNMENT Colored Facial Cosmetics 


Mascara composition 

Water-resistant mascaras typically deliver a combination of 
waxes, polymers, and pigments in a water-based emulsion 
to the lashes. The water helps contribute to the enhanced 
lash attributes by absorbing into the lash, bloating its diam¬ 
eter by as much as 30% and in many cases forcing the lashes 
to curl. The waxes are emulsified into the water creating a 
thick, creamy texture that glides onto the lashes in a thick 
film that resists fading, abrasion, and flaking throughout the 
day, but is still easily removed with warm water and soap. 
Polymers are often included to bind the mascara to itself as 
well as to the lashes. Advances in polymer technology over 
the last 20 years have led to very substantive films that last 
throughout the day, even though they are delivered to the 
lash in an aqueous medium. 

Consumers who desire the longest lasting mascara will 
select the anhydrous waterproof formulations which contain 
little to no water and deliver very durable, but difficult to 
remove films. Waterproof mascaras usually use hydrocarbon 
solvents and anhydrous raw materials. They provide a long- 
wearing film on the lashes, which is very resistant to water, 
smudging, and smearing. Its anhydrous nature makes it 
more difficult to both apply and remove, and it may have 
more eye irritation potential. A list of common water-resist¬ 
ant and waterproof mascara ingredients and their functions 
can be found in Table 23.2. 


Additional ingredients can be added to a formulation to 
enhance particular eyelash characteristics. A common 
method for producing lengthening mascara is to include 
fibers in the formulation so that, when applied, the fibers 
will extend beyond the natural ends of the eyelashes. 
Similarly, large, lightweight, hollow particles may be incor¬ 
porated into the mascara film to create a thicker film for 
bolder lashes. Synthetic or natural polymers with novel 
properties can also be incorporated to induce a curling effect 
on the lashes. 

Other forms of mascara are available such as clear mas¬ 
caras, waterproofing topcoats, pearlescent topcoats, and lash 
primers. This breadth of cosmetic options gives consumers 
many choices to groom and decorate their lashes. 

Mascara applicator technology 

Consumers will typically judge a better mascara applicator 
as one that creates more clumps of lashes that are uniformly 
spaced apart [10]. However, different consumers apply their 
mascara for different end looks - some aspiring for only a 
few (spiky) clumps of lashes, others working towards well- 
separated lashes. The twisted wire brush has been the main¬ 
stay mascara applicator for 30 years. As seen in Figure 25.2, 
it is simply a metal wire bent back upon itself into two paral¬ 
lel wires. Bristles, typically made of nylon, are inserted 
between the bent wire and it is twisted around to form a 


Table 25.2 Water-resistant and waterproof mascara ingredients and function. 


Class 

Material type 

Examples 

Function 

Water-resistant 

solvent 

Carrier fluid 

Water, propylene glycol 

Deliver mascara ingredients to lashes in 
liquid vehicle 

Waterproof solvent 

Carrier fluid 

Isododecane, cyclomethicone, 
petroleum distillates 

Deliver mascara ingredients to lashes in 
liquid vehicle 

Film former 

Polymers/binder 

Cellulosic polymers, acrylates 
co-polymer/xanthan or acacia gum 

The main constituent of the mascara film 
and serves to bind the other ingredients 
together in the wet and dried film 

Structurant 

Waxes/clays 

Beeswax, carnauba wax/bentonite 
clay 

Provides body and structure to the 
mascara film during application and wear 

Surfactant or 

emulsifier 

Anionic/non-ionic, etc. 

Sodium laureth sulfate/TEA soap, 
polysorbates 

In a formulation with two immiscible 

substances, an emulsifier stabilizes the 
two dissimilar parts of the formulation, 
preventing separation 

Colorant 

Pigments 

Iron oxides, mica, ultramarines 

Provides color to the mascara film 

Care or attribute 

Hair treatment/ 
lengthening, etc. 

Panthenol, keratin/nylon or silk fiber 

An ingredient included for a specific 
effect in the mascara film 

Preservatives 

Antimicrobial/pH 

adjuster/chelator 

Parabens, potassium sorbate/citric 
acid/EDTA 

Prevents contamination of harmful 
microorganisms such as bacteria, mold, 
and fungus 






192 





25. Eye cosmetics 


helical arrangement of bristles. The bristles are very effective 
at depositing mascara onto lashes, but the inconsistent 
spacing between bristles on the brush can lead to excessively 
large clumps of lashes, uneven lash separation, and the need 
for compensatory grooming of the lashes. 

The skill of the consumer plays a large part in achieving 
her desired look in a timely manner, and the twisted wire 
applicator has seen many adjustments over the years to 
make mascara application easier and quicker for consumers 
to achieve their desired lash appearance. Innovations include 
tapering the end of the applicator, curving the brush, hollow 



Figure 25.2 Twisted wire brush mascara applicators. 


bristles, changing the diameter or length of the applicator, 
and even cutting shapes out from the applicator's profile to 
create channels within the collection of bristles. Despite the 
wide variety of twisted wire applicator innovations, the bris¬ 
tles all converge around a central shaft and the spacing 
between adjacent bristles is highly variable. This limits the 
consistency of both lash clump size and gaps between clumps 
of lashes. 

In the last 5 years, technology advancements have enabled 
a whole new category of molded mascara applicators to 
emerge. The precisely engineered surfaces of a molded appli¬ 
cator, shown in Figure 25.3, give control over the place¬ 
ment, number, and physical properties of bristles or other 
grooming surfaces. The result is consistent gaps between 
bristles, enabling the bristles to penetrate deeper into the 
lashes for increased mascara transfer and more efficient and 
regular separation of lashes. In addition, the varieties of 
colors, shapes, and textures that can be created are almost 
limitless and offer new opportunities to delight consumers. 
A few examples of these are shown in Figure 25.4. 


Other eyelash treatments 

The ability to change the appearance of eyelashes extends 
beyond mascara. False eyelashes may be applied as entire 
strips or as individual groups of lashes. They are adhered to 
the eyelid with a non-permanent adhesive. This allows easy 
application and removal at the end of the day. 

Lash tinting involves application of a semi-permanent dye 
for color that lasts about a month. This is a two part product, 
just like permanent coloring for scalp hair. An oxidative 
cream is mixed with an oxidizing agent and then applied 


Figure 25.3 Molded mascara applicator 
with precisely engineered, parallel bristles. 



193 




















































ADORNMENT Colored Facial Cosmetics 





Figure 25.4 Various molded mascara applicator designs 
showing the wide range of possibilities that are possible 
with this emerging applicator type. 


onto the lashes and left for 15-20 minutes. The dye forms 
while it is penetrating into the lashes. 

Lash perming is achieved by rolling the lashes of the top 
eyelid around a thin cotton tube. The lashes are then coated 
with a high pH gel that penetrates into the lashes and breaks 
disulfide bonds holding together keratin protein strands in 
the cortex. After about 15 minutes, a second neutralizing 
coat is applied to the lashes to neutralize the high pH and 
reform bonds between protein strands to hold the lash in its 
new shape after the cotton cylinder is removed. 

Eyelash extensions are synthetic fibers that are bonded to 
individual lashes, usually with a cyanoacrylate adhesive. 
Typically, 30-80 lashes per eyelid will have eyelash exten¬ 
sions applied, and they typically last 1-2 months. 

Eyelash transplants involve relocating scalp follicles to the 
eyelids. Small incisions are made in the top and bottom 
eyelids into which are placed the transplanted follicles. 
Manual curling and trimming is necessary because the scalp 
follicles will continue to grow hair for years in a relatively 
straight direction. 

Blepharopigmentation, or eyelid tattooing, involves appli¬ 
cation of pigmentation into skin at the edges of the eyelid 
to simulate either eyeliner or the appearance of lashes. This 
is permanent but can be reversed with laser surgery. 

Over the past 3 years, a number of products have launched 
with claims that suggest physiologic stimulation of lash 
growth for darker, thicker, longer, and curlier lashes. Most 
of these make use of prostoglandin analogs that are typically 
used for treating glaucoma, but are known to have the 
above (beneficial) side effects [11]. 


Eyeshadow 

Eyeshadow is color applied to the upper eyelids. It is used 
to add depth and dimension to the eyes, thus drawing atten¬ 
tion to the eye look or eye color. The predominant form is 
powder, both pressed and loose, but eyeshadow is also avail¬ 
able in other forms, such as creams, sticks, and liquids. 
Eyeshadows are very similar to blushes and pressed powder 
in terms of their key ingredients (Chapter 22). They are 
usually comprised of pigments and pearls, and fillers bound 
together with a volatile or non-volatile binder. They may 
also contain other powder particles such as boron nitride or 
polytetrafluoroethylene to improve slip and pay-off on 
application. 


Eyeliners 

Eyeliner is used to outline the upper and lower eyelids. This 
serves to define the eyes against the backdrop of the face. 
Eyeliner can also be used to make the eye look more bold 
or to give the illusion of a different eye shape. They are 
typically available in liquid form and wood or mechanical 
pencils. Wood pencils excel at creating a softer, more natural 
look. Mechanical pencils tend to be a bit bolder, and the gel 
forms are good for gliding easily across the eyelid. Liquid 
liners can create a distinctively defined eye and provide 
longer wear but can be difficult to apply correctly. Most eye 
pencils are comprised of colorants dispersed in a waxy 


194 





25. Eye cosmetics 


matrix for ease of application and to help the color adhere 
to the skin. Liquid liners, although not as popular as the 
pencil form, contain colorants that are dispersed in volatile 
solvents so they can be applied with a brush or pen-like 
applicator. 


Product application 

Eyeshadow application techniques vary according to the 
look you are trying to achieve but, generally, an appealing 
look can be achieved using three complementary shades in 
light, medium, and dark. The lightest shade highlights the 
area below the eyebrow, the medium shade is applied to the 
creased area, and the darkest shade is reserved for the area 
immediately above the upper eyelashes. Matte, silky shadows 
tend to blend nicely and are better for mature eye skin than 
iridescent or sparkly shades which can highlight fine lines 
or puffiness. 

Generally, eyeliner is applied to the outer two-thirds 
of the lower lid below the lashes and to the entire upper 
lid above the lashes in a thin line. An angled brush can 
be used to gently soften the look. Although dark liners 
draw a lot of attention to the eyes, softer shades of brown, 
especially in the daytime, can be used to avoid looking 
too harsh. 

Curling the lashes with an eyelash curler prior to mascara 
application will make the eyes seem more wide open and 
bright. Usually, mascara is applied generously to upper 
lashes and to a lesser extent to the lower lashes. Color choice 
of mascaras can change the look obtained. For instance, on 
light-haired individuals brown mascara can be used for a 
softer, more natural look. Black or brown-black is best for 
deeper skin tones or for a more dramatic look. Figure 25.5 
shows the effect of applying eye cosmetics. 


Safety and regulatory considerations for 
eye area cosmetics 

Most countries or regions regulate cosmetics to a varying 
degree of complexity, largely because of safety considera¬ 
tions. Because cosmetics touch and interact directly with the 
human body, the various regulations are in place to ensure 
that consumers are not exposed to materials that may be 
harmful. This stems from various safety incidents that have 
occurred with personal care products. For instance, consum¬ 
ers can have allergic reactions to lash dyes, which were 
becoming a popular product in the 1930s. In one case, an 
allergic reaction to a lash dye led to one consumer becoming 
blind [4]. Ultimately this was one of many cases in the USA 
that led to Food and Drug Administration (FDA) overseeing 
of cosmetics. In particular, it led to a positive list of colorants 
that could be used for eye area cosmetics [12]. In later years, 
other regulatory bodies, such as the European Commission, 
adopted similar restrictions to the FDA's on colorants for use 
in the eye area [13]. 

Because of their intimate contact with the human body, 
all cosmetics should be adequately preserved from microbio¬ 
logic insults. This is especially true for eye cosmetics where 
contact with a contaminated product could lead to an 
eye area infection and the possibility of more serious 
complications. 


The future of eye cosmetics 

For a mature category such as eye cosmetics, it is surprising 
how much potential still exists for product innovation. 
New products are being introduced that feature enhanced 
long wear, new applicator surfaces, novel color effects, 



Figure 25.5 The impact of eye cosmetics on eye beauty, (a) Before, (b) After. 


195 







ADORNMENT Colored Facial Cosmetics 



Figure 25.6 Digital simulations of lashes aid cosmetic scientists in visualizing potential lash looks for product design. 


sustainable natural materials, improved application, and 
even lash growth. 

The mascara application experience is being improved 
with automated applicators that use vibrating or rotating 
brushes to take away some of the skill necessary to achieve 
beautiful lashes. These applicators can be held up against the 
lashes while they work for the consumer by exposing more 
of the applicator surface to the lashes, encouraging more 
deposition of mascara and more grooming of the lashes. 

Products are coming onto the market that claim to actually 
stimulate and enhance lash growth. While there are regula¬ 
tory considerations that make these products controversial, 
if approved for consumer use they may negate the need of 
some women to use mascara to achieve beautiful lashes. 

Scientists around the world are even starting to tap in to 
virtual modeling to peel back the individual factors of eye 
beauty, and to design looks not yet achievable with today's 
products. Three-dimensional modeling and simulation are 
being exploited to mimic consumers' real eyelashes, and 
then simulate how those lashes may be made more beauti¬ 
ful. For the first time we can explore both the true limits of 
eye beauty and the individual impacts of single lash variables 
(e.g. lash separation, thickness, lift, color, curl) on beauty. 
An optimized digital representation of a consumer's lashes 
can be used to design a formula and applicator to deliver the 
right personalized lash look for them. Figure 25.6 shows 
several related simulations where only lash clumping is 
adjusted [14]. 


References 

1 Kunzig R. (1999) Style of the Nile. Discover September, p. 80. 

2 Ahuja A. (1999) Chemistry and eye make-up - science. Times 
September 22. 

3 Geibel V. (1991) Mascara. Vogue August. 

4 Riordan T. (2004) Inventing Beauty: a history of the innovations 
that have made us beautiful. New York: Broadway Books, pp. 
1-31. 

5 Balaji Narasimhan R. (2001) Pearl luster pigments. In: Paintindia 
Vol. 51, pp. 67-72. 

6 Elder MJ. (1997) Anatomy and physiology of eyelash follicles: 
relevance to lash ablation procedures. Ophthal Plast Reconstr Surg 
13, 21-5. 

7 Na J, Kwon O, Kim B et al. (2006) Ethnic characteristics of 
eyelashes: a comparative analysis in Asian and Caucasian 
females. Br J Dermatol 155, 1170-6. 

8 Liotet S, Riera M, Nguyen H. (1977) Les cils: Physiologie, struc¬ 
ture, pathologie. Arch Opht 37, 697-708. 

9 http://www.atsdr.cdc.gOv/hac/hair_analysis/2.4.html. 

10 Sheffler RJ. (1998) The revolution in mascara evolution. Happi 
April, pp. 48-52. 

11 Wolf R, Matz H, Zalish M, Pollack A, Orion E. (2003) 
Prostaglandin analogs for hair growth: great expectations. 
Dermatology 9, 7. 

12 21C.F.R. Part 700, Subchapter G. 

13 Directive 76/768/EC, OJ L 262, p. 169 of 27.9.1976. 

14 Wyatt P, Vickery S, Sacha J. (2006) Poster given at SIGGRAPH 
2006. 


196 









Part 2: Nail Cosmetics 


Chapter 26: Nail physiology and grooming 

Phoebe Rich 1 and Heh Shin R. Kwak 2 

Oregon Dermatology and Research Center, Portland, OR, USA 
2 Knott Street Dermatology, Portland, OR, USA 


BASIC CONCEPTS 

• Knowledge of nail unit anatomy and physiology and an understanding of nail plate growth and physical properties are 
important prerequisites for understanding nail cosmetics. 

• Disruption and excessive manipulation of certain nail structures, such as the hyponychium and eponychium/cuticle, should be 
discouraged during nail cosmetic procedures and nail salon services. 

• In addition to beautifying natural nails, nail cosmetics are beneficial in camouflaging unsightly medical and infectious nail 
problems, especially during the lengthy treatment period. 

• Some nail cosmetics provide a protective coating for fragile, weak, and brittle nails. 

• Proper nail grooming is crucial for maintaining nail health. 

• Although most nail cosmetics are used safely, it is important to be aware of potential complications associated with nail 
cosmetic materials and application processes. 


Introduction: Nail physiology 

Nail unit anatomy 

Understanding nail unit anatomy is an essential first step to 
comprehending the complexity of nail cosmetics use, includ¬ 
ing pathology induced by cosmetic materials and proce¬ 
dures. The nail unit is composed of the nail matrix, proximal 
and lateral nail folds, the hyponychium, and the nail bed 
(Figure 26.1). 

Table 26.1 lists common nail signs and definitions relevant 
to nail cosmetics. 

Nail matrix 

The nail matrix is comprised of germinative epithelium from 
which the nail plate is derived (Figure 26.2). The majority 
of the matrix underlies the proximal nail fold. The distal 
portion of the nail matrix is the white lunula visible through 
the proximal nail plate on some digits. It is hypothesized that 
the white color of the lunula can be attributed to both 
incomplete nail plate keratinization and loose connective 
tissue in the underlying dermis. The proximal nail matrix 
generates the dorsal (superficial) nail plate, while the distal 
nail matrix generates the ventral (inferior) nail plate. This 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


concept is crucial to understanding nail pathology. Preserving 
and protecting the matrix during nail cosmetic processes is 
essential for proper nail plate formation. Significant damage 
to the nail matrix can result in permanent nail plate 
dystrophy. 

The nail plate is derived from the nail matrix and com¬ 
posed of closely packed, keratinized epithelial cells called 
onychocytes. Cells in the matrix become progressively flat¬ 
tened and broadened and lose their nuclei as they mature 
into the nail plate. The nail plate is curved in both the lon¬ 
gitudinal and transverse planes, allowing for adhesion to the 
nail bed and ensheathment by in the proximal and lateral 
nail folds. Longitudinal ridging may be present on both the 
dorsal and ventral surface of the nail plate. Mildly increased 
longitudinal ridging on the dorsal nail plate is considered a 
normal part of aging. Ridging on the ventral surface of the 
nail plate is caused by the structure of the underlying nail 
bed and vertically oriented blood vessels. The composition 
and properties of the nail plate are further discussed below. 

Nail folds 

The nail folds surround and protect the nail unit by sealing 
out environmental irritants and microorganisms through 
tight attachment of the cuticle to the nail plate. The cuticle 
is often cut or pushed back during cosmetic nail procedures 
which can allow moisture, irritants, bacteria, and yeasts 
under the nail fold, resulting in infection or inflammation 
of the nail fold, termed paronychia (Figure 26.3). Chronic 


197 








ADORNMENT Nail Cosmetics 


Table 26.1 Common nail signs associated with or helped by nail cosmetics. 


Nail sign 

Definition 

Association 

Onycholysis 

Separation of the nail plate from the nail bed 

Vigorous cleaning of hyponychium 
exacerbates. Polish hides 

Onychorrhexis 

Increased longitudinal ridging 

Associated with aging, distal notching. 
Polish may help 

Onychoschizia 

Lamellar splitting of the free end of the nail plate 


Paronychia 

Inflammation of the nail fold 


Dyschromia yellow 

Staining of the surface of the nail plate yellow 
from the dye in nail polish 


Green/black discoloration 

Pseudomonas is a bacteria that generates a 
green-black pigment that discolors the nail plate 


Nail bed changes as in psoriasis, 
onychomycosis 




Free edge 

Lunula 

\ 

of nail plate 

\ Cuticle 

Nail bed 

y^^^Proximal 


nail fold 

/ 


Hyponychium 

/ 


Distal groove 

Lateral nail fold 


Figure 26.1 Nail unit with lines indicating important structures. 


Nail matrix (nail root) 



t 


Figure 26.3 Paronychia. 


paronychia may disrupt the underlying nail matrix and sub¬ 
sequently lead to nail plate dystrophy. 

Hyponychium 

The hyponychium is the cutaneous margin underlying the 
free edge of the nail plate. The nail bed ends at the hypo¬ 
nychium. It is contiguous with the volar aspect of the 
fingertip. 

The hyponychium has a similar function as the cuticle and 
acts as an adherent seal to protect the nail unit. The hypo¬ 
nychium should not be overmanipulated during nail groom¬ 
ing to avoid onycholysis, or separation of the nail plate from 
the nail bed. This space created between the nail plate and 


198 


















26. Nail physiology and grooming 


bed retains moisture and establishes an environment for 
potential pathogens, such as yeast, bacteria, or fungi. 

Nail bed 

The nail bed is thin, 2-5 cell layer thick epithelium that 
underlies the nail plate. It extends from the lunula to the 
hyponychium. The nail bed is composed of longitudinal, 
parallel rete ridges with a rich vascular supply which is 
responsible for the pink coloration of the bed, as well as 
longitudinal ridges on the ventral surface of the nail plate. 
In chronic onycholysis the nail plate is separated from the 
nail plate for an extended duration, the nail bed epithelium 
may become keratinized, form a granular layer, and lead to 
permanent onycholysis (Figure 26.4). 

Other structures 

The distal phalanx lies immediately beneath the nail unit. 
The extensor tendon runs over the distal interphalangeal 
joint and attaches to the distal phalanx 12 mm proximal to 
the eponychium. Given that there is little space between the 
nail unit and distal phalanx, minor injury to the nail unit 
may extend to the periosteum and lead to infection. 

Nail growth 

Normal nail growth has been cited to vary from less than 
1.8 mm to more than 4.5 mm per month. Average fingernail 
growth is 0.1 mm per day, or 3 mm per month. This informa¬ 
tion is useful when determining the duration of nail pathol¬ 
ogy. For example, if splinter hemorrhages are located 6 mm 
from the proximal nail fold, it can be estimated that they 
occurred from injury approximately 2 months prior. Based 
on this growth rate, fingernails grow out completely in 
6 months. Toenails grow at one-third to half of the rate 
of fingernails and take 12-18 months to grow out 
completely. 


Several factors affect nail growth. Nail growth peaks at 
10-14 years and declines after 20 years. Nail growth is pro¬ 
portional to finger length, with fastest growth of the third 
fingernail and slowest growth of the fifth fingernail. Nails 
grow slower at night and during the winter. Other factors 
causing slower nail plate growth include lactation, immobi¬ 
lization, paralysis, poor nutrition, yellow nail syndrome, 
antimitotic drugs, and acute infection. Faster nail growth has 
been noted during the summer and in the dominant hand. 
Pregnancy, psoriasis, and nail biting are other factors linked 
to faster nail growth. Table 26.2 summarizes factors influ¬ 
encing nail growth. 

Physical properties of nails 

Nail composition 

The nail plate is composed mainly of keratin, which is 
embedded in a matrix of non-keratin proteins. There is wide 
variation in reported percentage of inorganic elements 
found in the nail plate. Several elements, including sulfur, 
calcium, iron, aluminum, copper, silver, gold, titanium, 
phosphorus, zinc, and sodium, are constituents of the nail 
plate. Of these elements, sulfur has the greatest contribution 
to nail structure and comprises approximately 5 % of the nail 
plate. Nail plate keratin is cross-linked by cysteine bonds, 
which contain sulfur. Some studies attribute brittle nails to 
decreased cysteine levels. 

There is a popular misconception that calcium content is 
responsible for nail hardness. This idea likely stems from 
knowledge that bone density is related to calcium intake. 
Calcium comprises less than 1% of the nail plate by weight. 
No evidence supports that decreased calcium is linked to 
brittle nails and that calcium supplementation increases nail 
strength. In fact, kwashiorkor, a nutritional deficiency 
caused by insufficient protein intake, is manifested by soft, 
thin nails and demonstrates increased nail plate calcium. 



Figure 26.4 (a & b) Onycholysis. 


199 






ADORNMENT Nail Cosmetics 


Table 26.2 Nail cosmetic products: ingredients and uses. 

Product 

Ingredients 

Application procedures 

Benefits of use 

Potential complications 

Nail polish 

Film former: nitrocellulose 
Thermoplastic resin: 

(toluene sulfonamide 
formaldehyde resin) 

Plasticizer: dibutyl pthalate 
Solvents and pigments 

Polish is applied in several 
coats with a small brush and 
allowed to dry by evaporation 

Provides an attractive glossy 
smooth decorative surface 
and camouflages nail defects 
Protects nail from 
dehydration and irritants 

Yellow staining of nail 
plate. Potential for allergy 
to toluene sulfonamide 
formaldehyde resin and 
other ingredients 

Nail hardener 

May contain formaldehyde 
in a nail polish base, also 
may have fibers that 
reinforce the nail 

Application similar to nail 
polish which is applied in 
several coats 

Forms several layers of 
protection on the nail plate 

Potential allergy to 
formaldehyde and 
possible brittleness 

Acrylic nail 
extensions 

Acrylic monomer, polymer, 
polymerized to form a 
hard shell attached to the 
nail plate or to a plastic tip 
glued to the nail 

Monomer (liquid) and 
polymer (powder) mixed to 
form a paste and polymerized 
with a catalyst to a harden 
the product 

Cover unsightly nail defects, 
may help manage 
onychotillomania and habit 
tic disorder 

Possible allergy to 
acrylates, inflexibility of 
artificial nail may cause 
injury to nail unit 

Cuticle remover 

Contains potassium 
hydroxide or sodium 
hydroxide plus humectants 

Applied to cuticle for 5-10 
minutes to soften cuticle 
adhered to nail plate 

Gently removes dead skin 
attached to the nail plate 
without mechanical trauma 

Over removal of cuticle 

and result in the 
potential for paronychia 
and secondary bacteria 
and Candida infections. 

Can soften the nail plate 

Nail polish 

remover 

Acetone, butyl acetate, 
ethyl acetate, may also 
contain moisturizer such 
as lanolin or synthetic oils 

Wiped across nail plate with 
cotton or tissue to remove 
nail polish 

Removes polish smoothly 
without removing layers of 
nail plate 

May dehydrate the nail 
plate and periungual 
tissue 


Water content of the normal nail plate is reported to range 
between 10% and 30%. The most commonly accepted value 
is 18% water content in normal nails and 16% in brittle 
nails. However, a study aimed at confirming this demon¬ 
strated no statistically significant difference between normal 
and brittle nails [1]. In addition, this study showed lower 
water content than previously thought, with a mean water 
content of 11.90% in normal nails and 12.48% in brittle 
nails. Some limitations in this study were noted, including 
analysis of only the distal nail plate. In addition, the time 
between sample collection and analysis was variable, with 
an average of 24 hours, and a subanalysis demonstrated loss 
of water content varied significantly between those samples 
analyzed at 1 and 24 hours. 

Lipids, including squalene and cholesterol, are also con¬ 
stituents of the nail plate and comprise 3 % of the nail plate 
by weight. These lipids are thought to diffuse from the nail 
bed to the nail plate. 

Nail flexibility 

Most references to nail strength and hardness actually refer 
to nail flexibility. A flexible nail will bend and conform to 


physical force, whereas a hard nail will break and become 
brittle. Nail flexibility is aided by plasticizers, which are 
liquids that make solids more flexible. Examples of nail 
plasticizers are water and lipids. Flexibility is decreased by 
solvents, such as nail polish removers, which remove both 
water and lipids, and detergents, which remove lipids. 

Nail brittleness is caused by loss of flexibility. Brittle nails 
are a common complaint and are found in 20% of the 
general population and more commonly in females (Figure 
26.3). Brittleness encompasses several nail features includ¬ 
ing onychoschizia which is lamellar peeling of distal nail 
plate (Figure 26.6), splitting and notching sometimes associ¬ 
ated with ridges, and fragility of the distal nail plate, lamellar 
splitting of the free end of the nail plate. Several attempts 
have been made to define brittleness with objective meas¬ 
urements, including Knoop hardness, which evaluates 
indentation at a fixed weight; modulus of elasticity, which 
describes the relationship between force/area and deforma¬ 
tion produced; tensile strength; and a brittleness grading 
system. 

Although there are systemic and cutaneous conditions 
that may cause brittle nails, exogeneous causes are more 


200 





26. Nail physiology and grooming 



Figure 26.6 Onychoschizia, distal lamallar peeling of the nail plate. 


201 












ADORNMENT Nail Cosmetics 


(a) 


(b) 



Figure 26.7 (a) Manicure; (b-d) Pedicure. 




common. These include mechanical trauma, exposure to 
solvents and extraction of plasticizers, and repeated hydra¬ 
tion and drying of nails. 

Nail thickness 

Thickness of the nail plate is determined primarily by matrix 
length and rate of growth. Measurements of distal plate 
thickness demonstrate greatest thickness in the thumbnail, 
followed by the second, third, fourth, and fifth fingernails. 
Thickness also is influenced by sex, with males having an 
average nail plate thickness of 0.6 mm, compared to 0.5 mm 
in females. 


Nail grooming principles 

Nail care 

Several principles of nail care should be observed during nail 
grooming to maintain normal nail structure. 


Manicure and pedicures are the process of grooming the 
fingernails and toenails respectively at home or in a nail 
salon (Figure 26.7). The procedure involves soaking the 
nails to soften prior to trimming and shaping the nail plate. 
Excess cuticle is removed from the nail plate using a chemi¬ 
cal cuticle remover and often a metal implement. The nails 
are then finished with a shiny, smooth coat of nail enamel, 
commonly called nail polish, sandwiched between a base 
coat and top coat, or the nails may be buffed to a soft luster. 

Other procedures such as acrylic gel or silk wrap enhance¬ 
ments may be added to the basic manicure. These nail 
extension procedures involve applying product to the 
natural nail or to a plastic tip glued to the nail. The material 
are applied and shaped before curing or polymerizing to 
form a hard surface. 

Nail trimming 

Most nail experts advocate shaping nails with an emery 
board rather than clipping or cutting nails. Filing should be 


202 









26. Nail physiology and grooming 


carried out with the file exactly perpendicular to the nail 
surface to avoid inducing onycholysis. Proper filing of the 
free edge of nail plate reduces sharp edges that may catch 
and cause nail plate tearing, if nails must be clipped or cut, 
this should be performed after they have been hydrated 
which maximizes nail flexibility and prevents breakage 
during trimming. Nails should also be kept as short as pos¬ 
sible. Long nails, especially those that are brittle, may act as 
a lever and create onycholysis. 

Nail buffing and filing 

The dorsal nail plate surface is often filed to remove shine 
from the natural nail plate at nail salons prior to application 
of nail products or artificial nails. Care must be taken to 
avoid excessive filing, especially with electric drills. The nail 
plate is approximately 100 cell layers thick. If filing must be 
done, only 5 % of the nail plate thickness, or approximately 
five cell layers, should be removed which is just enough to 
remove the shine of the dorsal nail plate in order to facilitate 
adherence of the product to the nail plate. Limited buffing 
to reduce nail ridging is acceptable, but excessive buffing 
thins the nail plate and should be avoided. 

Care for brittle nails 

Brittle nails should be treated by avoiding nail trauma and 
increasing flexibility. Nails should be kept short. This pre¬ 
vents lifting of the nail plate, disruption of the hypony- 
chium, and onycholysis. In addition, nails should be trimmed 
after they have been hydrated and are the most flexible. 
Moisturizing the nail plate increases flexibility and helps 
avoid brittle nails. Some experts recommend moisturizing 
up to four times daily. Avoiding solvents and frequent 
hydration and dessication of nails also helps maintain flex¬ 
ibility. There is controversy regarding avoidance of nail cos¬ 
metics in the management of brittle nails. Some believe that 
nail polish is protective and seals the moisture in the nail 
plate by preventing rapid evaporation. Nail polish also pro¬ 
tects the nail plate from some environmental irritants. There 
is some concern that overuse of nail polish remover will 
dehydrate the nail and exacerbate brittleness. 

Biotin has also been advocated for brittle nails, but results 
are inconclusive. The recommended dose is 2.5-5 mg/day, 
which is 100-200 times the recommended daily allowance. 
Given that biotin has relatively few side effects, most experts 
recommend its use, in addition to the above grooming 
recommendations. 

Adverse effects from nail grooming 

Nail cosmetics are safely used by millions of people world¬ 
wide. In addition to enhancing the appearance of normal 
nails, cosmetics are useful for improving the appearance of 
unsightly nail dystrophy caused by medical disease, such as 
psoriasis (Figure 26.8), onychomycosis (Figure 26.9), or 
trauma. Although nail cosmetics rarely cause problems, it is 




Figure 26.9 Onychomycosis. 


important to be aware of possible adverse effects related to 
procedures or to materials used in nail cosmetics (Figure 
26.10). 

Allergic reactions to nail cosmetic ingredients 

The most common allergen in nail polish is toluene sulfona¬ 
mide formaldehyde resin with sensitization occurring in 
up to 3% of the population. Other potential allergens are 
cyanoacrylate nail glue, formaldehyde in nail hardeners, and 
ethylmethacrylate in sculptured nails. Allergic contact der¬ 
matitis from nail cosmetics is seen on periungual skin, as 
well as the eyelids, face, and neck, caused by touching these 
areas with freshly polished fingernails (Figure 26.11). 

Irritant reactions 

Common nail products that cause irritant reactions include 
acetone or acetate nail polish removers and cuticle removers 


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ADORNMENT Nail Cosmetics 



Figure 26.10 Yellow staining from nail polish. 


with sodium hydroxide. Reactions are manifested as an irri¬ 
tant dermatitis of the periungual skin and as brittle nails, 
including onychoschizia. Prolonged use of nail polish induce 
keratin granulations on the nail plate. This commonly is 
seen when fresh coats of nail enamel are applied on top of 
old enamel for several weeks. These granulations cause 
superficial friability of the nail plate (Figure 26.12). 

Nail cosmetic procedures 

Several nail problems, including paronychia, onycholysis, 
and thinning of the nail plate, may be mechanically induced 
by cosmetic procedures. Paronychia, or inflammation of 
the proximal nail fold, is often caused by cutting or pushing 
back the cuticle, leading to separation of the proximal 
nail fold and the nail plate. Sharp manicure instruments 
used to clean under the nail plate may induce onycholysis 
and create an environment for secondary bacterial and 



Figure 26.11 Allergic contact dermatitis from nail cosmetics, (a) On the eyelid, (b) On periungal skin caused by acrylates. 



Figure 26.12 (a & b) Keratin granulations. 


204 










26. Nail physiology and grooming 



Figure 26.13 Infection caused by Pseudomonas. 


fungal infection. Onycholysis may be exacerbated by long 
artificial nails because of increased mechanical leverage. 
Nail drills or excessive filing and buffing may lead to 
thinning of the nail plate and brittle nails. Breaks in the 
integrity of the nail unit allow access of microorganisms 
such as Candida and Pseudomonas (Figure 26.13) and result 
in exacerbation of paronychia and onycholysis. Some basic 
principles for safe use of nail cosmetics are outlined in 
Table 26.3. 


Conclusions 

Nail cosmetics is a multibillion dollar industry which con¬ 
tinues to grow. Thorough knowledge of nail anatomy and 
physiology is essential for the safe use and development of 
nail cosmetics. 


Table 26.3 Information for patients for safe nail cosmetic use. After 
Rich [2], 


• Be sure that the salon sterilizes instruments, preferably with an 
autoclave. Some salons offer instruments for clients to purchase 

• Stinging, burning, or itching following a nail salon treatment may 
be signs of an allergic reaction to a cosmetic ingredient. Remove 
the product and seek medical evaluation by a dermatologist 

• If using artificial nail extensions, keep them short. Long nails can 
cause mechanical damage to the nail bed. Remove extensions at 
the first sign of onycholysis and avoid enhancements until the nail 
is reattached 

• Do not allow nail technician to cut or clip cuticles. Cuticles serve an 
important function and should not be cut. They may be pushed 
back gently with a soft towel after soaking the nails or bathing 


References 

1 Stern DK, et al. (2007) Water content and other aspects of brittle 
versus normal fingernails. J Am Acad Dermatol 57, 31-36. 

2 Rich R (2001) Nail cosmetics and camouflaging techniques. 
Dermatol Ther 14, 228-36. 

Further reading 

Chang RM, Hare AQ, Rich P. (2007) Treating cosmetically induced 
nail problems. Dermatol Ther 20, 54-9. 

Baran R, Dawber RPR, de Berker DAR, Haneke E, Tosti A. (2001) 
Diseases of the Nails and their Management, 3rd edn. Malden, MA: 
Blackwell Science. 

DeGroot, AC, Weyland JW. (1994) Nail cosmetics. In: Unwanted 
Effects of Cosmetics and Drugs used in Dermatology, 3rd edn. New 
York, Oxford: Elsevier, 524-9. 

Draelos Z. (2000) Nail cosmetic issues. Dermatol Clin 18, 675-83. 
Iorizzo M, Piraccini B, Tosti, A. (2007) Nail cosmetics in nail disor¬ 
ders. J Cosmet Dermatol 6, 53-6. 

Paus R, Peker S, Sundberg JP. (2008) Biology of hair and nails. In: 
Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology, 2nd edn. 
Elsevier, pp. 965-86. 

Rich P. (2008) Nail surgery. In: Bolognia JL, Jorizzo JL, Rapini RP, 
eds. Dermatology, 2nd edn. Elsevier, pp. 2259-68. 

Schoon DD. (2005) Nail Structure and Product Chemistry, 2nd edn. 
Thompson Corporation. 

Scher RK, Daniel CR. (2005) Nails: Diagnosis, Therapy, Surgery, 3rd 
edn. Elsevier. 


205 





Chapter 27: Colored nail cosmetics and hardeners 

Paul H. Bryson and Sunil J. Sirdesai 

OPI Products Inc, Los Angeles, CA, USA 


BASIC CONCEPTS 

• Nail lacquers contain resins that create a thin, resistant film over the nail plate. 

• Adding color to the nail plate surface is accomplished with a variety of nail lacquers including a basecoat, color coat, and 
topcoat. 

• Nail hardeners cross-link nail protein to increase strength, but overuse may contribute to brittle nails. 

• Nail lacquers are resistant to contamination and cannot spread nail infectious disease. 


Introduction 

The use of colored nail polish and nail hardeners has 
increased among consumers with the rise of the manicure 
industry. With nail salons found in almost every strip mall, 
painting nails is a very popular service for the customers of 
the professional manicurist. The use of nail cosmetics is well 
rooted in history. Ancient Chinese aristocrats colored their 
nails red or black with polishes made with egg white, bees 
wax, and gelatin. The Ancient Egyptians used henna to dye 
the nails a reddish brown color (J. Spear, editor of Beauty 
Launchpad , Creative Age Publications, Van Nuys, CA, per¬ 
sonal communication). In the 19th and early 20th centuries, 
"nail polish" was a colored oil or powder, which was used 
to rub and buff the nail, literally polishing and coloring the 
nail simultaneously. Modern nail polish was created in the 
1920s, based on early nitrocellulose-based car paint technol¬ 
ogy [!]• 

The term "nail polish" is somewhat of a misnomer for 
modern products, because no actual polishing is involved in 
its application. The product is composed of dissolved resins 
and dries to a hard, glossy coat, so the technically correct 
name is "nail lacquer." However, the terms "nail polish," 
"nail enamel," "nail varnish," "nail paint," and "nail lacquer" 
are used interchangeably. Several specialty products have 
developed from nail lacquer, including basecoats, topcoats, 
and hardeners. A newer technology involves pigmented UV- 
curable resins. This chapter discusses the current use of these 
modern formulations (Table 27.1). 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


Application techniques 

These nail products are applied by painting the nail with 
a brush. In best manicuring practices, old nail lacquer is 
removed with a solvent followed by application of a base- 
coat, two coats of colored nail lacquer, and a topcoat allow¬ 
ing sufficient time for drying between coats. The basecoat 
increases the adhesion of the colored nail lacquer to the 
nail while the topcoat increases the chip-resistant charac¬ 
teristics of the colored nail lacquer. These products are 
applied on both natural and artificial nails. Nail hardener 
is only applied to natural nails, either as a basecoat or a 
stand alone product. UV-curing nail "lacquers" are hard¬ 
ened with a UV light after application; no evaporation is 
necessary. In all cases, best practice dictates that the prod¬ 
ucts be kept off the skin. Failure to do so can result in 
eventual, irreversible sensitization and allergic contact der¬ 
matitis [2]. 

Proper nail cosmetic application dictates the maintenance 
of excellent hygiene in the nail salon. Unsanitary procedures 
may result in medical problems [3]. Nail technicians must 
use cleaned, disinfected, or disposable nail files and tools. 
Clipping or cutting the cuticles before applying nail lacquer 
can also lead to infection. Infections with staphylococcus [4] 
and herpetic whitlows [3] have been attributed to unsani¬ 
tary manicures. Nail technicians should not perform services 
on diseased nails. 


Lacquers, topcoats, and basecoats 

Nail lacquers contain six primary ingredients: resins, sol¬ 
vents, plasticizers, colorants, thixotropic agents, and color 
stabilizers. By law, all ingredients must be disclosed on the 


206 








27. Colored nail cosmetics and hardeners 



Figure 27.1 Lacquered nails. Reproduced by permission of OPI 
Products, Inc. 




Figure 27.3 Be careful with the cuticle. Reproduced by permission of 
OPI Products, Inc. 


Table 27.1 Overview of product types. 


Product class 

Nail lacquer 

Basecoat 

Topcoat 

Nail hardener 

UV curable 

Coating created by 

Solvent 

evaporation 

Solvent evaporation 

Solvent evaporation 

Mainly solvent 
evaporation; some 
polymerization of 
formalin may occur 

Polymerization 

Resin type or mix 

Balanced 

Biased toward 

adhesion 

Biased towards 
glossiness, hardness 

Balanced or biased 

towards adhesion 

Balanced; resin formed by 
reacting directly on nail 

Pigment 

Yes 

Little or none 

Little or none 

Usually none 

Yes 

Removal 

Easily dissolves in 
solvent 

Easily dissolves in 
solvent 

Easily dissolves in 
solvent 

Easily dissolves in 
solvent 

Soften by acetone soak, 
then peel 

Benefits 

Attractive color; 
can be applied 
over natural nails 

or enhancements 

Helps color coat 
last longer; 
protects natural 
nail from staining 

Helps color coat last 
longer; some contain 
optical brighteners 
or UV protectants 

Strengthens natural 
nail by cross-linking 
proteins; may be 
used as a basecoat 

Attractive color; tough 
cured-in-place resin 
protects nail 


207 





ADORNMENT Nail Cosmetics 



Figure 27.4 Infected nail. Reproduced by permission of Nails Magazine. 


product packaging, usually by means of the International 
Nomenclature for Cosmetic Ingredients (INCI) names. 
Understanding the chemistry nomenclature is important for 
isolating the causes of allergic contact dermatitis. Each of 
these ingredients is discussed in detail. 

Resins 

Resins hold the ingredients of the lacquer together while 
forming a strong film on the nail. Chemically, the resins are 
polymers - long-chain molecules - that are solid or gummy 
in their pure state. Two types of resins are used. Hard, glossy 
resins give the lacquered nail its desired appearance; these 
include nitrocellulose and the methacrylate polymers or 
co-polymers (usually labeled by their generic INCI name, 
"acrylates co-polymer"). Topcoat formulations have a higher 
percentage of these harder resins. Softer, more pliable resins, 
which enhance adhesion and flexibility, include tosylamide/ 
formaldehyde resin, polyvinyl butyral, and several polyester 
resins. Basecoats incorporate a higher proportion of pliable 
resins. Of all the resins, tosylamide/formaldehyde resin is 
the most commonly implicated in allergic reactions [6] 
affecting not only the fingers, but other parts of the body by 
transfer [7]. 

Solvents 

Solvents are the carriers of the lacquer. They must dissolve 
the resin, suspend the pigments, and evaporate leaving a 
smooth film. The drying speed must be controlled to prevent 
bubbling and skinning, thus faster drying is not necessarily 
better. Optimum drying speed requires a careful blend of 
solvents. Ethyl acetate, n-butyl acetate, and isopropyl alcohol 
are common solvents, other acetates and alcohols are also 



occasionally employed. All solvents have a dehydrating and 
defatting action on the skin, but this usually occurs during 
the removal of the lacquer, not its application. 

Formerly, toluene was a commonly used solvent, but the 
industry trend is to move away from it in response to 
expressed health concerns. Research indicates that toluene 
exposure for a nail technician and consumer is far below 
safe exposure limits [8]; however, consumer perceptions are 
negative for toluene, necessitating its replacement. A related 
chemical, xylene, has already virtually vanished from the 
industry. Ketones such as acetone or methyl ethyl ketone 
are not amenable to suspension of pigments and are there¬ 
fore used at low levels, if at all, in lacquers, although these 
substances will dissolve the resins effectively and therefore 
are useful as lacquer removers. 

A few water-based nail lacquers are now on the market. 
Because of their much slower drying time they are unlikely 
to replace solvent-based products in the foreseeable future. 
If they are ever perfected, they will completely take over the 
industry, because water is cheaper, non-flammable (which 
reduces shipping costs), and odorless. 

Plasticizers 

Plasticizers keep the resins flexible and less likely to chip. 
Camphor and dibutyl phthalate (DBP) have long been used 
for this purpose; however, the EU maintains its 2004 ban of 
DBP, despite authoritative findings regarding its safety in 
nail lacquer [9]. Because many manufacturers sell globally, 
DBP has largely been replaced by other plasticizers, includ¬ 
ing triphenyl phosphate, trimethyl pentanyl diisobutyrate, 
acetyl tributyl citrate, ethyl tosylamide, and sucrose 
benzoate. 

Colorants 

Colorants are selected from among various internationally 
accepted pigments. They are mostly used in the "lake" form. 


208 





27. Colored nail cosmetics and hardeners 



Figure 27.6 Nail lacquer. Reproduced by permission of OPI Products, Inc. 

meaning that the organic colorants have been adsorbed or 
co-precipitated into inorganic, insoluble substrates such as 
the silicates, oxides, or sulfates of various metals. A shimmer 
effect is created by minerals such as mica, powdered alumi¬ 
num, or polymer flakes. Guanine from fish scales is falling 
out of favor but is still occasionally used. 

Following INCI convention, most colorant materials are 
labeled by their international "Color Index" (Cl) numbers. 
This is a convenient way to identify colors, which have dif¬ 
ferent national designations. Labeling colorants by their Cl 
numbers is either legal or de facto accepted by most regula¬ 
tory agencies around the world; even so, out of deference 
to local custom, colors are often declared binonially (e.g. Cl 
77891/Titanium Dioxide). 

However, because of space limitations, lacquer manufac¬ 
turers may declare only the Cl numbers on the bottle - often 
on a small peel-off sticker at the bottom of the bottle. This 
can pose a problem as few nail lacquer users are aware that, 
for example, "Cl 60725" means the same as "D&C Violet #2" 
(USA) or "Murasaki 201" (Japan). Fortunately, the full des¬ 
ignations of the colors are usually listed on the box (which 
has more space than the bottle) and/or the Material Safety 
Data Sheet (MSDS). If these are unavailable, a web search 
or a phone call to the manufacturer is usually sufficient to 
obtain this information. 

Another difficulty with international designations is that 
some closely related colorant chemicals and their lakes are 
lumped under one Cl number. An example is the ubiquitous 
Cl 15850, which covers D&C Red #6, D&C Red #7, and all 
the various lakes of both. Normally, the manufacturer can 
provide more specific information if needed. 

Colorants sometimes cause staining of the nail. Although 
uncommon, it is more often seen with colors at the red end 


of the spectrum. It can usually be prevented by using a 
basecoat between the lacquer and the natural nail [10]. 
Topcoats can also cause apparent yellowing, but this is 
usually the product rather than the natural nail - as can be 
easily seen by removing the product [10]. 

Thixotropic agents 

Thixotropic agents provide flow control and keep the lacquer 
colorants dispersed. They are usually clay derivatives such as 
stearalkonium bentonite or stearalkonium hectorite. Most 
topcoats and basecoats are uncolored and do not require 
these additives. Silica is also sometimes used as a thickener. 

Color stabilizers 

Color stabilizers, such as benzophenone-1 and etocrylene, 
are added to prevent color shifting of the lacquer on expo¬ 
sure to UV light. These substances are better known as 
sunscreens, but their use in nail lacquer is to protect the 
color. Some specialty topcoats have a high level of UV pro¬ 
tectants, for application over colored nail lacquer to prevent 
fading during tanning booth use. 

Minor ingredients 

Minor ingredients may include vitamins, minerals, vegetable 
oils, herbal extracts, or fibers such as nylon or silk. Some 
companies may include adhesion-enhancing agents in lac¬ 
quers or basecoats, or other proprietary ingredients whose 
functions they elect not to disclose (Table 27.2). 

Antifungal agents 

Antifungal agents may be added to nail lacquer for thera¬ 
peutic purposes. However, as of this writing, there is only 
one prescription US Food and Drug Administration (FDA) 
approved antifungal nail lacquer, a topical solution of 8% 
ciclopirox (Penlac®, Sanofi-Aventis, Bridgewater, NJ, USA). 
According to FDA Consumer Magazine , "There are no approved 
nonprescription products to treat fungal nail infections ... 
fungal infections of the nails respond poorly to topical 
therapy ... the agency ruled that any OTC product labeled, 
represented or promoted as a topical antifungal to treat 
fungal infections of the nail is a new drug and must be 
approved by FDA before marketing" [11]. Furthermore, the 
FDA's policy is to "prohibit claims that nonprescription 
topical antifungals effectively treat fungal infections of the 
scalp and fingernails" [12]. 

Preservatives 

Preservatives are not present in nail lacquer. Regulatory 
authorities inquired if microbial cross-contamination could 
occur when the same nail lacquer bottle and brush are used 
on multiple clients. In response, a series of experiments was 
performed to investigate microbe survival in nail lacquer. 
The results indicate that nail lacquers do not support micro- 


209 


ADORNMENT Nail Cosmetics 


Table 27.2 Common ingredients of nail lacquer and related products. 


Ingredient category and examples 

Function 

Hard resins 

Nitrocellulose 

Gloss 

Acrylates co-polymer 

Toughness 

Soft resins 

Tosylamide/formaldehyde resin 

Flexibility 

Polyvinyl butyral 

Adhesion 

Solvents 

Ethyl acetate 

Carrier for the resin and pigment 

Butyl acetate 

Removing lacquer 

Isopropyl alcohol 

Acetone (removers only) 

Soaking and removing UV-cured colors 

Monomers and oligomers 

Polyurethane acrylate oligomer 

Hardens to hold color on nail 

Hydroxypropyl methacrylate 

Various other acrylates and methacrylates 

Only in UV-curable colors, not standard lacquer 

Photoinitiators 

Benzoyl isopropanol 

Initiates the light cure reaction 

Hydroxycyclohexyl phenyl ketone 

Only in UV-curable colors, not standard lacquer 

Colorants 

FDA/EU approved colorant 

Mica 

Esthetic 

Plasticizers 

Camphor 

Dibutyl phthalate (formerly) 

Keeps resin flexible to prevent chipping 

Thixotropic agents 

Stearalkonium hectorite 

Controls flow 

Stearalkonium bentonite 

Suspends pigment until use 

UV stabilizers 

Benzophenone-1 

Etocrylene 

Prevents light-induced color fading 

Hardeners 

Formalin 

Hardens nail protein by cross-linking 

Dimethyl urea 

Only in hardener products 

Hydrolyzed proteins 

Keratin 

Thought to bond with formalin and nail protein 

Wheat, oats, etc. 

Usually used in hardeners 


bial growth in the laboratory or salon (OPI Products Inc., 
and Nail Manufacturers Council, unpublished data) [13]. 
The solvents are sufficiently hostile to microbes that no 
preservative is required. This does not apply to water-based 
products, because water is required for microbial growth. 
Although solvent-based water-free lacquer is hostile to 
microbes, it would be a mistake to assume that it has any 
curative value for nail fungus or other infections. 


Nail hardeners 

Modern nail hardeners are quite a contrast to an antique 
method of nail hardening which used fire. On the early 
American frontier, the combat sport called "rough and 
tumble" or "gouging" allowed fingernails to be used as 
weapons, and expert "gougers" hardened their nails by 


210 






27. Colored nail cosmetics and hardeners 


heating them over candles [14]. The heat of the candle flame 
caused cross-linking of the nail proteins. 

Modern nail hardeners contain a chemical cross-linking 
agent. Otherwise, their composition is similar to ordinary 
nail lacquer. As with lacquers, care must be taken to avoid 
skin contact during application to avoid allergic sensitiza¬ 
tion, particularly to the most common hardener, formalin 
(which is mistakenly equated with "formaldehyde" under 
current labeling rules.) Formalin cross-links proteins prima¬ 
rily by reacting with their nitrogen-containing side groups, 
forming methylene bridges [15]. Overuse causes too many 
cross-links, reducing the flexibility of the protein and causing 
brittleness, yellowing, and cracking of the nails. Manufacturers 
generally recommend avoiding overuse by cycling the prod¬ 
ucts, alternating between the hardener and a non-hardening 
topcoat every week or two. 

Other hardeners include dimethyl urea (DMU), which is 
does not cross-link as aggressively as formalin. It is also less 
allergenic [16]. Glyoxal, a relative of formaldehyde, is larger 
and less able to penetrate the skin, also contributing to 
reduced allergenicity. Hydrolyzed proteins are common 
additives in hardeners and may chemically bond to the for¬ 
malin. Many nail hardeners are simply clear lacquers with 
no cross-linking agents at all. These products rely on the 



Figure 27.7 Brittle nail. Reproduced by permission of Nails Magazine. 


strength of the resins to protect the nails. Until DMU or some 
other alternative proves itself, the most effective nail hard¬ 
eners will likely continue to rely on formalin. 


Formaldehyde issues 

Formalin, formaldehyde, and tosylamide/formaldehyde 
resin warrant some additional discussion. True formalde¬ 
hyde is a highly reactive gas. Obviously, it cannot be a part 
of nail products in that form. It is therefore combined with 
water to make a product traditionally called "formalin." 
Formalin contains water and a reaction product of water 
and formaldehyde, properly known as methylene glycol. 
Published literature [17] on the hydration of formaldehyde 
reveals a chemical equilibrium constant for this reaction, 
which confirms the near complete conversion of formalde¬ 
hyde to methylene glycol. This chemical equilibrium con¬ 
stant yields the presence of 0.0782% free formaldehyde in 
formalin. A nail hardener that is 1.5% formalin, the typical 
upper limit, therefore contains less than 0.0012% or 12 parts 
per million of formaldehyde. This is not to dismiss "formal¬ 
dehyde allergy", which causes significant suffering to some 
patients, but it would be more accurately known as meth¬ 
ylene glycol or formalin allergy (Figure 27.8). 

Unlike formaldehyde, methylene glycol is non-volatile; 
this explains why a California study showed that formalde¬ 
hyde gas levels in nail salons were not above the normal 
background levels found in other settings such as offices [8]. 
This is significant because the only identified cancer risk 
associated with formaldehyde exposure results from inhala¬ 
tion in industrial settings [18], not cosmetic skin or nail 
exposure. 

Tosylamide/formaldehyde resin is also a cause for contro¬ 
versy solely because of the word "formaldehyde" in its 
name. It is an inert macromolecule, created by reacting 
tosylamide and formaldehyde. However, the formaldehyde 
is consumed in the reaction, and any leftover formaldehyde 
is hydrated to methylene glycol by the water molecules 
generated in the reaction. Hence the formaldehyde content 
of the resin is essentially nil. However, allergies nevertheless 
occur; it has been speculated that trace formaldehyde is 



Figure 27.8 Formaldehyde versus methylene glycol. Reproduced 

by permission of OPI Products, Inc. Formaldehyde (gas) Methylene glycol (liquid) 


211 






ADORNMENT Nail Cosmetics 



Figure 27.9 Tosylamide formaldehyde resin. 
Reproduced by permission of OPI Products, Inc. 


responsible but sensitization to tosylamide/formaldehyde 
resin can occur in the absence of formaldehyde sensitization 
[19,20], and tests indicate that side products of the synthesis 
reaction can be responsible for the resin allergies [21] (Figure 
27.9). 

A final concern occasionally raised regarding formalde¬ 
hyde is its absence. Because formaldehyde-releasing agents 
have a long history as preservatives in other forms of cos¬ 
metics, it is sometimes mistakenly assumed that formalde¬ 
hyde was added to nail lacquer for preservative purposes. 
As a result, publicity regarding "formaldehyde-free" 
products has inspired fears of microbial cross-contamination 
via nail lacquer brushes. As noted above, experiments 
have shown that solvent-based nail lacquer is hostile to 
microbes and needs neither formaldehyde nor any other 
preservative. 


UV-cured "lacquers" 

UV-cured nail enhancements are discussed elsewhere 
(Chapter 28); however, a relatively new class of UV-curing 
nail "lacquers" merits mention here. The same pigments are 
used as in standard nail lacquer but instead of a solvent/resin 
base, curable methacrylate or acrylate oligomers and mono¬ 
mers are used. A photoinitiator causes polymerization of the 
monomers on exposure to UV light, leaving a polymer/ 
pigment coat. Unlike the products to create nail enhance¬ 
ments, these curable colored products are not used to sculpt 
nails, but are designed to apply as a thin coat of color, resem¬ 
bling conventional lacquer. 

Allergic sensitization may result from repeated skin expo¬ 
sure to uncured or incompletely cured monomers; the fully 
cured coat is inert. Good manicuring technique can mitigate 
this risk, but once an allergy is established it is irreversible. 
Allergies to the photoinitiators and pigments are also 
possible. The low-power UVA lamps used to activate the 
photoinitiator are comparable to summer sunshine [10], 
so the 1-3 minute curing time poses no hazard to healthy 
skin (Table 27.3). 


Table 27.3 Common health effects of nail color ingredients. 


Ingredients 

Health concerns 

Resins 

Possible allergies, particularly to 
tosylamide/formaldehyde resin 

Solvents 

Dehydration and defatting of skin 
and nails 

Irritant dermatitis 

UV-curable 

Allergy after repeated exposure to 

acrylates/methacrylates 

uncured monomer or oligomer 

Photoinitiators 

Possible allergies 

Possible photosensitization 

Colorants 

Occasional staining 

Occasional allergies 

Plasticizers 

Possible allergies 

Camphor exposure is contraindicated 
for some patients with fibromyalgia 

Thixotropic agents 

None known 

UV stabilizers 

Possible allergies 

Hardeners (cross-linkers) 

Formalin sensitization and allergies 

are common 

Overuse may cause brittleness or 
splitting of nail 

Not recommended for nails that are 
already brittle 

Hydrolyzed proteins 

Possible allergies 

May trigger gluten sensitivity via 
transfer to mouth 


Nail lacquer removers 

In contrast to nail enhancements for nail elongation pur¬ 
poses, no polymerization takes place during the drying of 
nail lacquer; the resin is simply deposited on the nail as the 


212 

















27. Colored nail cosmetics and hardeners 



Figure 27.10 UV curing lamp. Reproduced by permission of OPI 
Products, Inc. 

solvent evaporates. Therefore, removing nail lacquer is easy: 
it can be redissolved and wiped off with a solvent-soaked 
cloth pad, tissue, or cotton ball. Any solvent that dissolves 
the resin, and is safe for skin exposure, can be successfully 
used. Although UV-curable nail colors are polymerized, they 
are far less cross-linked than enhancements, and can be 
removed with a short acetone soak. 

Acetone, chemically known as dimethyl ketone or 2- 
propanone, is the preferred solvent, because it is the least 
physiologically hazardous. Other removers are based on 
ethyl acetate or methyl ethyl ketone (MEK). Ethyl acetate 
has the advantage of not damaging acrylic nails, so it is used 
for removing lacquer from nail elongation enhancements. 
However, because of air quality regulations in California, 
ethyl acetate, MEK, and most other acetone alternatives are 
prohibited for nail lacquer removers, and other states and 
countries are considering similar actions. Acetone is exempt 
because its atmospheric breakdown produces less photo¬ 
chemical smog than almost any other solvent. One other 
"clean air" solvent, methyl acetate, is allowed in California, 
but has been avoided by most manufacturers because of 
toxicity concerns; those who use it add an embittering agent 
to deter accidental ingestion. Other hazardous solvents such 
as methanol and acetonitrile are seldom used, and are not 
California-compliant (Figure 27.11). 

All solvents can have significant drying and defatting 
effects on the skin, leading to irritation. This can be miti¬ 
gated by using a lacquer remover with added moisturizers, 
or by using lotion afterwards. Drying and cracking of the 
nail can also result; oiling the nail is the most common way 
to counteract this. Some removers contain fragrances or 
botanical additives, which may pose allergy risks. 

Low-odor, non-volatile removers have been created based 
on methylated vegetable oils and/or various dibasic esters. 
As with water-based nail lacquer, however, the slow speed 
of nail polish removal with these products prevents them 
from finding general marketplace acceptance. These prod¬ 
ucts are less damaging to the skin barrier. 



Figure 27.11 Polish remover in action. Reproduced by permission of 
OPI Products, Inc. 


Conclusions and future developments 

Arguably the largest potential for future improvement lies 
in cleaner application techniques, not new products. As 
more cases of manicure-transmitted infection are publicized, 
customers and governments will demand that nail techni¬ 
cians practice proper sanitation and disinfection. 

Most manufacturers are looking to develop "greener" 
products, whether in perception or reality. The trends away 
from toluene and DBP will surely continue, as will efforts 
to find a functional substitute for formalin. As for removers, 
most likely only acetone will survive the regulatory con¬ 
cerns. Water-based and UV-cured products have the poten¬ 
tial to reduce solvent emissions, but still have unresolved 
disadvantages compared to traditional lacquers. Research 
continues in realm of nail polish as adding nail color is com¬ 
monly practiced form of adornment. 

References 

1 Gorton A. (1993) History of nail care. Nails , February. Torrance, 
CA: Bobit Business Media. 

2 Schultes SE. (Ed.) (2007) Miladay's Standard Nail Technology, 5th 
edn. New York: Thomson Delmar Learning, pp. 129-32. 

3 Baran R, Maibach HI. (2004) Textbook of Cosmetic Dermatology . 
New York: Taylor & Francis, p. 295. 

4 Lee W. (2005) Bill targets nail salon outbreaks. Los Angeles Times , 
August 25, p. B-l. 

5 Anon. (2002) Nightmare manicure: woman who says she got 
herpes from manicure is awarded $3.1 million ABCNews.com , 
May 29. 

6 Linden C, Berg M, Farm G, Wrangsjo K. (1993) Nail varnish 
allergy with far reaching consequences. Br JDermatol 128, 57-62. 

7 Frosh PJ, Menne T, Lepoittevin JP. (2006) Contact Dermatitis, 4th 
edn. Basel: Birkhauser, p. 499. 


213 



ADORNMENT Nail Cosmetics 


8 McNary JE, Jackson EM. (2007) Inhalation exposure to formal¬ 
dehyde and toluene in the same occupational and consumer 
setting. Inhalat Toxicol 19, 573-6. 

9 Dibutyl phthalate - Summary risk assessment (2003, with 2004 
addendum), European Commission Joint Research Centre, 
Institute for Health and Consumer Protection, European 
Chemicals Bureau, Italy. 

10 Schoon DD. (2005) Nail Structure and Product Chemistry , 2nd edn. 
New York: Thomson Delmar Learning. 

11 Kurtzweil P. (1995) Fingernails: Looking good while playing 
safe. FDA Consumer Magazine, December. 

12 US Food And Drug Administration (1993) Answers , September 
3. Available from: http://www.fda.gov/bbs/topics/ANSWERS/ 
ANS00529.html; retrieved September 3, 2008. 

13 Nail Manufacturers Council (NMC) data, publication 
forthcoming. 

14 Fischer DH. (1989) Albion's Seed: Four British Folkways in America. 
Oxford: Oxford University Press, p. 738. 

15 Kiernan JA. (2000) Formaldehyde, formalin, paraformaldehyde 
and glutaraldehyde: What they are and what they do. Microscopy 
Today 00-1, 8. 

16 Schoon DD. (2005) Formaldehyde vs. DMU; What's the Difference? 
Vista, CA: Creative Nail Design. Available from: www. 


beautytech.com/articles/out.php?ID=354; retrieved August 25, 
2008. 

17 Winkelman JGM, Voorwinde OK, Ottens M, Beenackers AACM, 
Janssen LPBM. (2002) Kinetics and chemical equilibrium of 
the hydration of formaldehyde. Chem Engineering Sci 57, 
4067-76. 

18 International Agency for Research on Cancer (IARC) - 
Summaries & Evaluations (Group 2A) (1995) Formaldehyde. 
62, 217. Available at: www.inchem.org/documents/iarc/vol62/ 
formal.html; retrieved July 4, 2009. 

19 Fuchs T, Gutgesell C. (1996) Is contact allergy to toluene 
sulphonamide-formaldehyde resin common? Br J Dermatol 135, 
1013-14. 

20 Final Report on Hazard Classification of Common Skin Sensitisers 
(January 2005), National Industrial Chemicals Notification and 
Assessment Scheme, Australian Government, Department of 
Health and Ageing, p. 106. 

21 Hausen BM, Milbrodt M, Koenig WA. (1995) The allergens of 
nail polish. (I). Allergenic constituents of common nail polish 
and toluenesulfonamide-formaldehyde resin (TS-F-R), Contact 
Dermatitis 33(3), 157-64. 


214 


Chapter 28: Cosmetic prostheses as artificial 
nail enhancements 


Douglas Schoon 

Schoon Scientific and Regulatory Consulting, Dana Point, CA, USA 


BASIC CONCEPTS 

• Artificial nail enhancements are commonly used to address malformed fingernails. 

• The major forms of artificial nail enhancements include nail wraps, liquid and powder, or UV gels. 

• Methacrylate monomer liquid systems remain the most widely used type of artificial nail enhancement. 

• Proper application of artificial nail enhancements can avoid infection and sensitization. 


Introduction 

The natural nail plate can not only be cosmetically elongated 
and enhanced to beautify the hands, but also to effectively 
address discolored, thin, and weak or malformed fingernails. 
When used properly, these cosmetic products and services 
provide great value and enhance self-esteem. Artificial nails 
not only add thickness and strength to the nail plate, they 
extend its length, typically 0.25-0.75 inches. A skilled nail 
technician can closely mimic the length and shape of the 
final product to create natural-looking artificial nails. Certain 
techniques utilizing custom blending of colored products 
allow the appearance of the nail bed to be extended beyond 
its natural boundary, which can dramatically lengthen the 
appearance of the fingers (Figure 28.1). 

A typical nail salon client wears artificial nail products to 
correct problems they are having with their own natural 
nails such as discoloration, splitting, breaking, unattractive 
or deformed nails (i.e. median canal dystrophy or splinter 
hemorrhages). There are several basic types from which to 
choose: nail wraps, liquid and powder, or UV gels. An over¬ 
view of each type is given in Table 28.1. 


Liquid and powder 

Liquid and powder systems ("acrylic nails") were the origi¬ 
nal artificial nail enhancements. These systems were similar 
to certain dental products made from methacrylate mono¬ 
mers and polymers. Methacrylates are structurally different 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


from acrylates, have different safety profiles, and should not 
be confused with one another. The literature frequently 
confuses methacrylates with acrylates and/or incorrectly 
suggests they are a single category (i.e. [meth] acrylate). The 
first structure shown in Figure 28.2 has a branching methyl 
group (-CH3) attached to the double bond of ethyl meth¬ 
acrylate. The branching changes both the size (10% larger) 
and shape of the methacrylate molecule, which reduces the 
potential for skin penetration. This helps explain why meth¬ 
acrylate monomers are less likely to cause adverse skin reac¬ 
tions than homologous acrylate monomers (i.e. ethyl 
acrylate and ethyl methacrylate). It is also one important 
reason why artificial nails containing acrylates are more 
likely to cause adverse skin reactions than those based solely 
on methacrylate monomers [1]. 

Methacrylate monomer liquid systems remain the most 
widely used type of artificial nail enhancement in the world. 
The "liquid" is actually a complex mixture of ethyl methacr¬ 
ylate (60-95%) and other di- or tri-functional methacrylate 
monomers (3-5%) that provide cross-linking and improved 
durability, inhibitors such as hydroquinone (HQ) or methyl 
ether hydroquinone (MEHQ) (100-200p.p.m.), UV stabiliz¬ 
ers, catalysts such as dimethyl tolyamine (0.75-1.25%), 
flexibilizing plasticizers and other additives. The "powder" 
component is made from poly methyl and/or ethyl meth¬ 
acrylate polymer beads (approximately 50-80pm), coated 
with 1-2% benzoyl peroxide as the polymerization initiator, 
colorants, opacifiers such as titanium dioxide, and other 
additives. 

Liquid and powder systems are applied by dipping a brush 
into the monomer liquid, wiping off the excess on the inside 
lip of a low volume container (3-5 mL) called a dappen dish. 
The excess monomer is removed by wiping the brush on the 
edge of the dappen dish. The tip of the brush is drawn 
through the polymer powder, also in a dappen dish, and a 
small bead or slurry forms at the end of the brush. Three to 


215 







ADORNMENT Nail Cosmetics 


Table 28.1 The three main types of artificial nail enhancements. 


Type 

Chemistry 

Also known as 

Hardener 

Nail wraps 

Cyanoacrylate monomers 

Fiberglass wraps, resin wraps, 

Spray, drops, powder, or fabric treated 



no-light gels, silk or paper wraps 

with an tertiary aromatic amine 

Liquid and powder 

Methacrylate monomers and 

Acrylic, porcelain nails, solar nails 

Polymer powder treated with benzoyl 


polymers 


peroxide; monomer liquid contains 
tertiary aromatic amine 

UV gels 

Urethane acrylate or urethane 

Gel nails 

Low-power UVA lamp to activate the 


methacrylate oligomers/monomer 

UV gels 

photoinitiator and tertiary aromatic 



Soak-off gels 

amine catalyst 




Figure 28.1 The use of custom-blended colored powders with 
methacrylate monomers to "illusion sculpt" and extend the apparent 
length of a short nail bed while also correcting a habitually splitting nail 
plate. (Courtesy Creative Nail Design, Inc., Vista, CA, USA.) 

six beads are normally applied and smoothed into shape 
with the brush. Pink powders are applied over the nail bed 
and white powders are used to simulate the free edge of the 
nail plate. The slurry immediately begins to polymerize and 
hardens on the nail within 2-3 minutes. Over 93% of the 
polymerization occurs in the first 5-10 minutes, but com¬ 
plete polymerization can take 24-48 hours [2]. After hard¬ 
ening, the nail is then shaped either by hand filing or with 


an electric file to achieve the desired length and shape. The 
finished nail can be buffed to a high shine or nail color 
applied. 

Length is added to the nail plate in one of two ways: 

1 Adhering an ABS plastic nail tip to the nail plate with a 
cyanoacrylate adhesive, coating the tip with the liquid and 
powder slurry, and filing as described above. This technique 
is called "tip and overlay." 

2 A non-stick (Mylar® or Teflon® coated paper) form is 
adhered underneath the free edge of the natural nail and 
used as a support and guide to which the liquid and powder 
slurry is applied, then shaped and filed. This technique is 
called "nail sculpting." 

Proper preparation of the natural nail's surface is the key 
to ensuring good adhesion. Before the service begins, natural 
nails should be thoroughly scrubbed with a clean, disin¬ 
fected, soft-bristled brush to remove contaminants from the 
service of the nail plate as well as underneath the free edge 
(Figure 28.3). This removes surface oil and debris that can 
block adhesion. The nail is then lightly filed with a low grit 
abrasive file (f 80-240 grit) to increase surface area for better 
adhesion. Nail surface dehydrators containing drying agents 
such as isopropyl alcohol are applied to remove surface 
moisture and residual oils. Adhesion promoting "primers" 
are then applied to increase surface compatibility between 
the natural nail and artificial nail product. These adhesion 
promoters contain proprietary mixtures of hydroxylated 
monomers or oligomers, carboxylic acids, etc. In the past, 
methacrylic acid was frequently used but has fallen out of 
favor because of its potential as a skin and eye corrosive [3]. 


UV gels 

Products that cure under low intensity UVA lights, typically 
433-323nm, to create artificial nails are called "UV gels." 
UVB and UVC are not used to create UV gel nails [4]. Unlike 
liquid and powder systems, UV gels are not mixed with 


216 






28. Artificial nail enhancements 



Ethyl methacrylate Ethyl acrylate 

Figure 28.2 Chemical structure differences 
between methacrylates and acrylates. 


L 6 H 10 U 2 

Molecular weight 114 Daltons 


l 5 h 8 u 2 

Molecular weight 100 Daltons 



Figure 28.3 Equipment used to create liquid and powder artificial nails. 
1, Nail scrub brush; 2, dappen dishes containing liquid and powder; 

3, Mylar nail form; 4, abrasive files; 5, nail enhancement application 
brush; 6, ABS preformed nail tips; 7, plastic-backed cotton pad; 8, Nitrile 
gloves; 9, N-95 dust mask. (Courtesy Paul Rollins Photography, Inc. 
Laguna Niguel, CA, USA.) 


another substance to initiate the curing process. Historically, 
UV gels have been blends of polymerization photoinitiators 
(1-4%), urethane acrylate oligomers, and durability improv¬ 
ing, cross-linking monomers (approximately 75-95%), and 
catalysts such as dimethyl tolyamine (0.75-1.25%). Newer 
formulations using urethane methacrylate oligomers and 
monomers lower the potential for adverse skin reactions. 

Rate of cure is a hindrance for UV-curable artificial nails. 
Slow cure rates allow atmospheric oxygen to prevent curing 


of the uppermost layers of UV gel products. This layer can 
also be observed with certain types of liquid monomers: 
"odorless" products that utilize hydroxyethyl or hydroxy- 
propyl methacrylate as the main reactive monomer. This 
residual sticky surface layer is called the "oxygen inhibition 
layer" [5]. 

UV gels can be clear, tinted, or heavily colored. The natural 
nail is cleaned, filed, dehydrated, and coated with adhesion 
promoters. The UV gel is then applied to the nail, shaped, 
and finished in the same fashion as two-part liquid and 
powder systems and produces very similar looking results. 
In most cases, the same equipment used to create other 
types of artificial nails is used (Table 28.2). A notable excep¬ 
tion is UV gel curing achieved by placing the artificial nail 
under a UVA lamp for 2-3 minutes per applied layer. 
Because UVA does not efficiently penetrate more than a few 
millimeters into the UV gel, these products are applied and 
cured in several successive layers. UV gels are also applied 
over ABS nail tips or non-stick nail forms to lengthen the 
appearance of the natural nail. 


Nail wraps 

Methyl and ethyl cyanoacrylate monomer is used not only 
for adhering ABS nail tips to the natural nail, but also to 
create artificial nail coatings called "nail wraps." This tech¬ 
nique is not widely used, but accounts for at least 1 % of the 
worldwide market [6]. 

The natural nail is precleaned, shaped, and filed as 
described above, but the cyano functional group provides 
tremendous adhesion to the natural nail plate, eliminating 
the need for adhesion-promoting primers (Figure 28.4). Nail 
enhancements relying on cyanoacrylate monomers do not 
contain other cross-linking monomers and therefore are 
inherently weaker than cross-linking artificial nail enhance¬ 
ment systems. To improve durability and usefulness, a 
woven fabric (silk, linen, or fiberglass) is impregnated with 
cyanoacrylate monomer and adhered to the nail plate. Even 
so, these types of coatings are not strong enough to be 
sculpted on a non-stick nail form and cannot be extended 
beyond the free edge of the natural nail plate, unless the 


217 









ADORNMENT Nail Cosmetics 


Table 28.2 Specialized equipment used to create artificial nail enhancements. 

Item 

Description 

Brush 

Natural or synthetic hair brush for application, spreading, and shaping 
of monomer and oligomers products on the nail plate 

Dappen dish 

Small containers that hold liquid artificial nail monomer, oligomers, or 
polymer powders during the application process 

Manual files 

Wooden or plastic core boards coated with abrasive particles (e.g. 
silicon nitride, aluminium oxide or diamond) used to shape, shortening, 
smooth, thin, or buff both natural and artificial nails 

Electric files 

Handheld, variable speed, rotary motors that securely hold barrel-shaped 
abrasive bits and are use for the same purposes as manual files 

Nippers 

Small clippers sometimes used to remove old artificial nail product from 
the nail plate 

Wood stick 

A thin, pencil-shaped, plastic implement used to remove cuticle tissue 
from the nail plate 

Buffers 

Block shape, high grit abrasive buffers use for shape refining (180-240 
grit) or buffing to a high shine (>1000 grit) 

UV lamp 

Electrical device that holds either 4 or 9W UVA producing bulbs and is 
used to cure UV gel nail products 

Cotton pads 

Disposable pads or balls used to remove old nail polish and/or dusts 
after filing 

Scrub brush 

Soft bristle, disinfectable brushes used to clean natural and artificial nails 

Nail forms 

Mylar® or Teflon® coated paper used as a support and guide to 
extending artificial nails beyond the natural nail's free edge 

Nail tips 

Preformed ABS plastic tips adhered to the natural nail to support 
artificial nail products and create nail extensions beyond the nail's free 
edge 

Wrap fabric 

Loosely woven silk, linen, or fibreglass strips adhered to the natural nail 
plate with cyanoacrylate monomer to create nail wraps 

Droppers 

Used to transfer product from larger containers into dappen dishes or to 
apply nail wrap curing accelerators 

Scissors 

Slightly curved blades use for trimming or cutting natural nails and wrap 
fabrics 

Disinfectant container 

Containers designed to hold EPA registered disinfectants needed to 
properly disinfectant tools and implements 

Remover bowl 

Container that holds solvents (e.g. acetone) for artificial nail removal 



nail wrap is applied over an ABS nail tip, as previously 
described. Usually, cyanoacrylate monomers are very low 
viscosity, mobile liquids, but they are sometimes thickened 
with polymers (e.g. polymethyl methacrylate) and used 
without a reinforcing fabric. Such systems are referred to as 
"no-light gels." 

Cyanoacrylate monomers are applied without the use of 
a brush, directly from the container's nozzle and will cure 


upon exposure to moisture in the nail plate, but the process 
can be greatly hastened by solvent mixtures containing a 
tertiary aromatic amine such as dimethyl tolylamine (0.5- 
1%), which is either sprayed on, applied with an dropper, 
or impregnated into the woven fabric. After curing (5-10 
seconds), the nail wrap coating can be shaped and buffed to 
a high shine or nail color applied. This technique is also used 
to mend cracks or tears in the nail plate, by using the 


218 





28. Artificial nail enhancements 



Figure 28.4 Materials needed to apply nail wraps. 1, Abrasive file for 
nail preparation and final shaping; 2, scissors for cutting fabric; 3, block 
buffer for high-shining; 4, cyanoacrylates; 5, spray-on catalyst; 6, silk 
fabric; 7, pusher to gently remove skin from the nail plate. (Courtesy Paul 
Rollins Photography, Inc. Laguna Niguel, CA, USA.) 

cyanoacrylate monomer to adhere a small piece of fabric 
over the broken or damaged area of the plate. 


Artificial nail removal 

Improper removal of artificial nails can lead to nail damage; 
however, they can be safely removed if the proper proce¬ 
dures are followed. Acetone (dimethyl ketone) is the pre¬ 
ferred remover for artificial nail products, but methyl ethyl 
ketone (MEK) is also used. The artificial nails are placed in 
a small bowl and immersed in solvent. Nail wraps are the 
easiest to remove because they are not cross-linked poly¬ 
mers and have lower solvent resistance. They usually require 
less than 10 minutes immersion for full removal. Liquid and 
powder products are cross-linked polymers and can take 
30-40 minutes to remove. UV gels are also cross-linked and 
these urethane acrylate or methacrylate based artificial nails 
have inherently greater solvent resistance so removal can 
take 43-60 minutes. The removal process is greatly acceler¬ 
ated by prefiling to remove the bulk of the artificial nail. 
Improper removal can cause significant damage to the nail 
plate. Prying or picking off the artificial nails can lead to 
onycholysis [7]. A common myth is that artificial nail should 
be regularly removed to allow nails to "breathe"; in reality 
they should only be removed when there is a need. Frequent 
removal is not advised. 


Rebalancing 

As the natural nail grows, the artificial nail advances leaving 
a small space of uncoated nail plate. Every 2-3 weeks the 



Figure 28.5 Example of an adverse skin reaction caused by repeated 
contact to the skin. (Courtesy Paul Rollins Photography, Inc. Laguna 
Niguel, CA, USA.) 


nail technician will file the artificial nail down to one-third 
its thickness, reapply fresh product, and reshape the artificial 
nail, thereby covering the area of new growth. This process 
is called "rebalancing" and is essential to maintaining the 
durability and appearance of the artificial nail. 

"Soak-off gels" are highly plasticized, which softens the 
coating, making it more susceptible to solvent removal. This 
type of artificial nail often has low durability and therefore 
must be frequently removed and replaced, which can lead 
to excessive nail damage. 


Adverse reactions 

Both nail technicians and those wearing artificial nails can 
develop adverse skin reactions if steps are not taken to avoid 
prolonged and/or repeated skin contact with artificial nail 
products. For example, the product should be applied to the 
nail plate in such a manner that skin contact is avoided (i.e. 
a tiny free margin left between the eponychium and artificial 
nail). Typically, reactions are a result of many months of 
overexposure to eponychium, hyponychium, or lateral side 
walls (Figure 28.3). 

Reactions can appear as paronychia, itching of the nail bed 
and, in extreme cases, paresthesia and/or loss of the nail 
plate [8,9]. Onycholysis can be a result of allergic reactions, 
but the nail plate is resistant to penetration from external 
agents and this condition is more likely to be caused by 
overly heavy handed, aggressive filing techniques with 
coarse abrasives or overzealous manicuring of the hypony¬ 
chium area [10]. Allergic contact dermatitis can affect the 
chin, cheeks, and eyelids as a result of touching the face with 
the hands [11]. Filings and dusts may contain small amounts 
of unreacted monomers and oligomers, because it can take 


219 







ADORNMENT Nail Cosmetics 


24-40 hours for the artificial nails to finish the curing 
process. 

Nail technicians should be instructed to wash their hands 
thoroughly before touching the face or eye area. They 
should be warned to avoid contact with the dusts and filings, 
especially the oxygen inhibition layer created on the surface 
of UV gels and odorless monomer liquid systems (see above), 
which can contain substantial amounts of unreacted ingre¬ 
dients. Gloves (nitrile) and/or plastic-backed cotton pads 
should be used to remove the oxygen inhibition layer as skin 
contact should be avoided. The UV bulbs in the curing lamps 
should be changed every 2-4 months (depending on usage) 
to ensure thorough cure and lessen the amount of unreacted 
ingredients, thereby lowering the potential for adverse skin 
reactions. For liquid and powder systems, it is common for 
technicians to use excessive amounts of liquid monomer, 
creating a wet consistency bead. Nail technicians should 
avoid applying beads of product with a wet mix ratio because 
this can lower the degree of curing and increase the risk of 
overexposure to unreacted ingredients. Nail technicians 
should be instructed to avoid all skin contact with uncured 
artificial nail products or dusts and not to touch them to 
client's skin prior to curing. 


Nail damage and infection 

Avoiding the use of heavy grit abrasives (<180 grit) or elec¬ 
tric files directly on the nail plate will lessen the potential 
for damage and injury (e.g. onycholysis). Plate damage can 
occur when nail technicians aggressively file the natural 
nail, rather than use safer, smoother abrasive files (>180 
grit). These gentler methods also increase the surface area 
for better adhesion, but without overly thinning or damag¬ 
ing the nail plate. 

Methyl methacrylate (MMA) monomer is sometimes used 
illegally in artificial nail monomer liquids because of its low 
cost when compared to better alternatives (e.g. ethyl meth¬ 
acrylate [EMA]). MMA has very poor adhesion to the 
natural nail plate so technicians who use these liquid mono¬ 
mers frequently abrade away the uppermost layers of the 
natural nail plate to achieve significantly more adhesion by 
allowing for deposition into the more porous layers under¬ 
neath. However, this poor technique can compromise the 
nail plate's strength and durability, so liquid monomer 
MMA containing products should be avoided [12]. The 
other artificial nail systems described in this chapter have 
improved adhesion and do not require technicians to heavily 
abrade the nail plate in order to achieve proper adhesion. 

Infections can occur underneath the artificial nail to 
produce green or yellow stains (Figure 28.6). Several types 
of bacteria and dermatophytes can cause such infections 
(.Pseudomonas aeruginosa , Staphylococcus aureus , Trichophyton 
ruhrum). To avoid this, state regulations require nail techni- 


Figure 28.6 Example of an nail infection growing underneath an 
artificial nail. (Courtesy Paul Rollins Photography, Inc. Laguna Niguel, CA, 
USA.) 

cians to properly clean and disinfect all implements in an 
Environmental Protection Agency (EPA) registered disin¬ 
fectant to avoid transmission of pathogenic organisms, and 
to dispose of all single-use items. Clients should wash their 
hands, scrubbing under the nails with a clean and disin¬ 
fected, soft-bristled brush before receiving any services. 


Education 

Almost every US state requires specialized nail training and 
education, typically 300-750 hours depending on the state, 
to obtain a professional license and some states have con¬ 
tinuing education requirements. The textbooks teach a sur¬ 
prisingly wide range of topics including anatomy and 
physiology of the skin and nails, product chemistry, an over¬ 
view of common nail related diseases and disorders, con¬ 
tamination and infection control and universal precautions, 
safe working practices, as well as manicuring, pedicuring, 
and the artificial nail techniques described in this chapter 
[13-15]. 

Multilingual information sources for proper use and other 
safety information can be found from a wide range of 
sources, including the EPA [16] and Nail Manufacturers 
Council [17]. 

References 

1 Baran R, Maibach HE (2005) Cosmetics for abnormal and patho¬ 
logic nails. Textbook of Cosmetic Dermatology , 3rd edn. Taylor & 
Francis, London/New York, pp. 304-5. 

2 Schoon D. (1994) Differential scanning calorimeter determina¬ 
tions of residual monomer in ethyl methacrylate fingernail for¬ 
mulations and two addendums. Unpublished data submitted by 
the Nail Manufacturers Council to the Cosmetic Ingredient 
Review (CIR) Expert Panel. 

3 Woolf A, Shaw J. (1998) Childhood injuries from artificial nails 
primer cosmetic products. Arch Pediatr Adolesc Med 152, 41-6. 


220 





28. Artificial nail enhancements 


4 Newman M. (2001) Essential chemistry of artificial nails. The 
Complete Nail Technician. London: Thompson Learning, p. 41. 

5 Schoon D. (2005) Liquid and powder product chemistry. Nail 
Structure and Product Chemistry , 2nd edn. New York: Thomson 
Delmar Learning, p. 138. 

6 Kanerva S, Fellman J, Storrs E (1966) Occupational allergic 
contact dermatitis caused by photo bonded sculptured nail and 
the review on (meth) acrylates in nail cosmetics. Am J Contact 
Derm 7, 1-9. 

7 Schoon D. (2005) Trauma and damage. Nail Structure and Product 
Chemistry , 2nd edn. New York: Thomson Delmar Learning, 
p. 52. 

8 Fisher A, Baran R. (1991) Adverse reactions to acrylate sculp¬ 
tured nails with particular reference to prolonged paresthesia. 
Am J Contact Derm 2, 38-42. 

9 Fisher A. (1980) Permanent loss of fingernails from sensitization 
and reaction to acrylics in a preparation designed to make arti¬ 
ficial nails. J Dermatol Surg Oncol 6, 70-6. 

10 Baran R, Dawber R, deBerker D, Haneke E, Tosti A. (2001) 
Cosmetics: the care and adornment of the nail. Disease of the 


Nails and their Management , 3rd edn. Oxford: Blackwell Science, 
p. 367. 

11 Fitzgerald D, Enolish J. (1994) Widespread contact dermatitis 
from sculptured nails. Contact Derm 30, 118. 

12 Nail Manufactures Council (NMC). (2001) Update for Nail 
Technicians: Methyl Methacrylate Monomer. Scottsdale, AZ: 
Professional Beauty Association, www.probeauty.org/NMC 

13 Jefford J, Swain A. (2002) The Encyclopedia of Nails. London: 
Thompson Learning. 

14 Frangie C, Schoon D, et al. (2007) Milady's Standard Nail 
Technology , 5th edn. New York: Thomson Delmar Learning. 

15 Schoon D. (2005) Trauma and damage. Nail Structure and 
Product Chemistry , 2nd edn. New York: Thomson Delmar 
Learning. 

16 United States Environmental Protection Agency (2007) 
Protecting the Health of Nail Salon Workers, Office of Pollution 
Prevention and Toxics. EPA no. 774-F-07-001. 

17 Nail Manufacturers Council (NMC). A series of safety related 
brochures for nail technicians. Scottsdale, AZ: Professional 
Beauty Association. www.probeauty.org/NMC. 


221 


Part 3: Hair Cosmetics 


Chapter 29: Hair physiology and grooming 

Maria Hordinsky , 1 Ana Paula Avancini Caramori , 2 and Jeff C. Donovan 3 

department of Dermatology, University of Minnesota, Minneapolis, MN, USA 

department of Dermatology, Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil 

3 Division of Dermatology, University of Toronto, Toronto, Canada 


BASIC CONCEPTS 

• The hair follicle is a complex structure that produces an equally complex structure, the hair fiber. 

• Human hair keratins consist of at least 19 acidic and basic proteins which are expressed in various compartments of the hair 
follicle. 

• The science behind modern shampoos and conditioners has led to the development of rationally designed products for normal, 
dry, or damaged hair. 


Definitions 

The use of hair cosmetics is ubiquitous among men and 
women of all ages. Virgin hair is the healthiest and strongest 
but basic grooming and cosmetic manipulation cause hair to 
lose its cuticular scale, elasticity, and strength. Brushing, 
combing, and shampooing inflict damage on the hair shaft, 
much of which can be reversed with the use of hair condi¬ 
tioners. In this chapter, the physiology of hair, grooming 
techniques including the science and use of shampoos and 
conditioners, are reviewed. 


Physiology 
Hair follicle 

The hair follicle is a complex structure that demonstrates the 
ability to completely regenerate itself - hair grows, falls out 
and then regrows. Plucked hairs can regrow. Important cells 
for the development of hair follicles include stem cells in the 
bulge region and dermal papilla cells [1]. Hair follicle stem 
cells are described as being present just below the entrance 
of the sebaceous duct into the hair follicle. The hair follicle's 
complexity is further appreciated when examining the 
organization of follicles in the scalp and the complexity of 


Cosmetic Dermatology: Products and Procedures. Edited by Z.D. Draelos. 
©2010 Blackwell Publishing. 


its vascular complex and nerve innervation. Scalp hair fol¬ 
licles present in groups of one, two, three, or four follicular 
units (Figure 29.1). 

The hair follicle is defined histologically as consisting of 
several layers (Figure 29.2). It is the interaction of these 
layers that produces the hair fiber. The internal root sheath 
consists of a cuticle which interdigitates with the cuticle of 
the hair fiber, followed by Huxley's layer, then Henle's layer. 
Henle's layer is the first to become keratinized, followed by 
the cuticle of the inner root sheath. The Huxley layer con¬ 
tains trichohyalin granules and serves as a substrate for 
citrulline-rich proteins in the hair follicle. The outer root 
sheath has specific keratin pairs, K5-K16, characteristic of 
basal keratinocytes and the K6-K16 pair characteristic of 
hyperproliferative keratinocytes, similar to what is seen in 
the epidermis. Keratin K19 has been located in the bulge 
region [2,3]. 

The complexity of the hair follicle is further demonstrated 
by the fact the follicle cycles from the actively growing phase 
(anagen), through a transition phase (catagen), and finally 
a loss phase (telogen). The signals associated with the transi¬ 
tion from anagen, catagen to telogen are the subject of 
current research activities in this field. 

Product of the hair follicle: the hair fiber 

The hair follicle generates a complex fiber which may be 
straight, curly, or somewhere in between. The main con¬ 
stituents of hair fibers are sulfur-rich proteins, lipids, water, 
melanin, and trace elements. The cross-section of a hair 
shaft has three major components, from the outside to the 
inside: the cuticle, the cortex and the medulla [4]. 


222 









29. Hair physiology and grooming 



(b) 


Figure 29.1 (a) Horizontal section of a 4 mm scalp biopsy specimen demonstrating follicular units containing 1, 2, 3, or 5 anagen follicles, (b) Vertical 
section of a 4-mm scalp punch biopsy specimen from a normal, healthy Caucasian female in her early twenties. 



Fibers can be characterized by color, shaft shape - straight, 
arched, or curly - as well as microscopic features. The cuticle 
can be defined by its shape - smooth, serrated, or damaged, 
and whether or not it is pigmented. The cortex can be 
described by its color and the medulla by its distribution in 
fibers. It can be absent, uniform, or randomly distributed. 
Lastly, fibers can be abnormal and present with structural 
hair abnormalities such as trichoschisis or trichorrhexis 
nodosa. Both of these structural abnormalities can com¬ 
monly be seen in patients with hair fiber injury related to 
routine and daily cosmetic techniques including application 
of high heat, frequent perming as well as from weathering, 
the progressive degeneration from the root to the tip of 
the hair initially affecting the cuticle, then later the cortex 
[3]. 

The cuticle is also composed of keratin and consists of 6-8 
layers of flattened overlapping cells resembling scales. The 
cuticle consists of two parts: endocuticle and exocuticle. The 
exocuticle lies closer to the external surface and comprises 
three parts: b-layer, a-layer, and epicuticle. The epicuticle is 
a hydrophobic lipid layer of 18-methyleicosanoic acid on the 
surface of the fiber, or the f-layer. The cuticle protects the 
underlying cortex and acts as a barrier and is considered to 
be responsible for the luster and the texture of hair. When 
damaged by frictional forces or chemicals and subsequent 
removal of the f-layer, the first hydrophobic defense, the 
hair fiber becomes much more fragile. 

The cortex is the major component of the hair shaft. It lies 
below the cuticle and contributes to the mechanical proper¬ 
ties of the hair fiber, including strength and elasticity. The 
cortex consists of elongated shaped cortical cells rich in 


keratin filaments as well as an amorphous matrix of sulfur 
proteins. Cysteine residues in adjacent keratin filaments 
form covalent disulfide bonds, which confer shape, stability, 
and resilience to the hair shaft. Other weaker bonds such as 
the van der Waals interactions, hydrogen bonds and cou- 
lombic interactions, known as salt links, have a minor role. 
These bonds can be easily broken just by wetting the hair. 
It is the presence of melanin in the cortex that gives hair 
color; otherwise, the fiber would not be pigmented [4]. 

The medulla appears as continuous, discontinuous, or 
absent under microscopic examination of human hair fibers. 
It is viewed as a framework of keratin supporting thin shells 
of amorphous material bonding air spaces of variable size 
[4]. Fibers with large medullas can be seen in samples 
obtained from porcupines or other animal species. Other 
than in gray hairs, human hairs show great variation in their 
medullas. 

Human hair keratins 

Human hair keratins are complex and, until recently, 
research suggested that the hair keratin family consisted of 
15 members, nine type I acidic and six type II basic keratins, 
which exhibited a particularly complex expression pattern 
in the hair-forming compartment of the follicle (Figure 
29.2). However, recent genome analyses in two laboratories 
has led to the complete elucidation of human type I and II 
keratin gene domains as well as a completion of their com¬ 
plementary DNA sequences revealing an additional small 
hair keratin subcluster consisting of genes KRT40 and KRT39. 
The discovery of these novel genes brought the hair keratin 
family to a total of 17 members [3]. 


223 









Zones of mRNA/protein synthesis 


ADORNMENT Hair Cosmetics 



K39 




e 

f | 

CO 

CO 

1 

- 

\ 

J 

cu— 

mod 


d P 



dp 

K40 

K32+K40 



Figure 29.2 Schematic presentation of the complex pattern of hair keratin expression in the human hair follicle. (Reprinted by permission from 
Macmillan Publishers Ltd, J Invest Dermatol 127, 1532-5, 2007.) 


224 


*Zone of keratinization 
























































29. Hair physiology and grooming 


The human type II hair keratin subfamily consists of six 
individual members which are divided into two groups. 
Group A members hHbl, hHb3, and hHb6 are structurally 
related, while group C members hHb2, hHb4, and hHb5 are 
considered to be rather distinct. Both in situ hybridization 
and immunohistochemistry on anagen hair follicles have 
demonstrated that hHb5 and hHb2 are present in the early 
stages of hair differentiation in the matrix (hHb5) and cuticle 
(hHb5, hHb2), respectively. Cortical cells simultaneously 
express hHbl, hHb3, and hHb6 at an advanced stage of 
differentiation. In contrast, hHb4, has been undetectable in 
hair follicle extracts and sections, but has been identified as 
the most significant member of this subfamily in cytoskeletal 
extracts of dorsal tongue [3]. 


Grooming 

Shampoos: formulations and diversity 

Cleaning hair is viewed as a complex task because of the 
area that needs to be treated. The shampoo product has to 
also do two things - maintain scalp hygiene and beautify 
hair. A well-designed conditioning shampoo can provide 
shine to fibers and improve manageability, whereas a 
shampoo with high detergent properties can remove the 
outer cuticle and leave hair frizzy and dull. 

Formulations 

Shampoos contain molecules with both lipophilic and 
hydrophilic sites. The lipophilic sites bind to sebum and oil- 
soluble dirt and the hydrophilic sites bind to water, permit¬ 
ting removal of the sebum with water rinses. There are four 
basic categories of shampoo detergents: anionics, cationics, 
amphoterics, and non-ionics (Table 29.1). A typical shampoo 
will typically have two detergents. Anionic detergents have 
a negatively charged hydrophilic polar group and are quite 
good at removing sebum; however, they tend to leave hair 


Table 29.1 Four categories of shampoo detergents. 


1. Anionics 
Lauryl sulfate 
Laureth sulfates 
Sarcosines 
Sulfosuccinates 

2. Cationics 

3. Amphoterics 

Betaines such as cocamidopropyl betaine 
Sultaines 

Imidazolinium derivatives 

4. Non-ionics 


rough, dull, and subject to static electricity. In contrast, 
ampotheric detergents contain both an anionic and a cati¬ 
onic group allowing them to work as cationic detergents at 
low pH and as anionic detergents at high pH. Ampotheric 
detergents are commonly found in baby shampoos and in 
shampoos designed for hair that is fine or chemically treated 
[5]. 

The number of shampoo formulations on the market can 
be overwhelming but when the chemistry behind those 
marketed for "normal hair" or "dry hair" is understood, 
recommending the best product becomes easier (Table 29.2). 
Shampoos for "normal" hair typically have lauryl sulfate as 
the main detergent and provide good cleaning of the scalp. 
These are best utilized by those who do not have chemically 
treated hair. Shampoos designed for "dry hair" primarily 
provide mild cleansing but also excellent conditioning. An 
addition to shampoo categories has been the introduction of 
conditioning shampoos which both clean and condition. The 
detergents in these types of shampoos tend to be amphoter¬ 
ics and anionics of the sulfosuccinate type. These work well 
for those with chemically damaged hair and those who 
prefer to shampoo frequently. For individuals with signifi¬ 
cant sebum production, oily hair shampoos containing 
lauryl sulfate or sulfosuccinate detergents can work well but 
can by drying to the hair fiber. 

Hydrolyzed animal protein or dimethicone are added to 
conditioning shampoos, also commonly called 2-in-l sham¬ 
poos. These chemicals create a thin film on the hair shaft to 
increase manageability and even shine. For individuals with 
tightly kinked hair, conditioning shampoos with both clean¬ 
ing and conditioning characteristics that are a variant of the 
2-in-l shampoo can be beneficial. These shampoos can be 
formulated with wheatgerm oil, steartrimonium hydrolyzed 
animal protein, lanolin derivatives, or dimethicone and are 
designed for use either weekly or every 2 weeks. 

Conditioners 

Conditioners can be liquids, creams, pastes, or gels that func¬ 
tion like sebum, making hair manageable and glossy appear¬ 
ing. Conditioners reduce static electricity between fibers 
following co